TY  - JOUR
AU  - Krombholz, Richard
AU  - Fressle, Stefanie
AU  - Nikolić, Ines
AU  - Pantelić, Ivana
AU  - Savić, Snežana
AU  - Crevar-Sakač, Milkica
AU  - Lunter, Dominique
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4333
AB  - When it comes to skin penetration analysis of a topically applied formulation, the number of suitable methods is limited, and they often lack in spatial resolution. In vivo studies are pivotal, especially in the approval of a new product, but high costs and ethical difficulties are limiting factors. For that reason, good ex vivo models for testing skin penetration are crucial. In this study, caffeine was used as a hydrophilic model drug, applied as a 2% (w/w) hydrogel, to compare different techniques for skin penetration analysis. Confocal Raman microspectroscopy (CRM) and tape stripping with subsequent HPLC analysis were used to quantify caffeine. Experiments were performed ex vivo and in vivo. Furthermore, the effect of 5% (w/w) 1,2-pentanediol on caffeine skin penetration was tested, to compare those methods regarding their effectiveness in detecting differences between both formulations.
PB  - John Wiley and Sons Inc
T2  - Experimental Dermatology
T1  - ex vivo–in vivo comparison of drug penetration analysis by confocal Raman microspectroscopy and tape stripping
VL  - 31
IS  - 12
DO  - 10.1111/exd.14672
ER  - 

@article{
author = "Krombholz, Richard and Fressle, Stefanie and Nikolić, Ines and Pantelić, Ivana and Savić, Snežana and Crevar-Sakač, Milkica and Lunter, Dominique",
year = "2022",
abstract = "When it comes to skin penetration analysis of a topically applied formulation, the number of suitable methods is limited, and they often lack in spatial resolution. In vivo studies are pivotal, especially in the approval of a new product, but high costs and ethical difficulties are limiting factors. For that reason, good ex vivo models for testing skin penetration are crucial. In this study, caffeine was used as a hydrophilic model drug, applied as a 2% (w/w) hydrogel, to compare different techniques for skin penetration analysis. Confocal Raman microspectroscopy (CRM) and tape stripping with subsequent HPLC analysis were used to quantify caffeine. Experiments were performed ex vivo and in vivo. Furthermore, the effect of 5% (w/w) 1,2-pentanediol on caffeine skin penetration was tested, to compare those methods regarding their effectiveness in detecting differences between both formulations.",
publisher = "John Wiley and Sons Inc",
journal = "Experimental Dermatology",
title = "ex vivo–in vivo comparison of drug penetration analysis by confocal Raman microspectroscopy and tape stripping",
volume = "31",
number = "12",
doi = "10.1111/exd.14672"
}

Krombholz, R., Fressle, S., Nikolić, I., Pantelić, I., Savić, S., Crevar-Sakač, M.,& Lunter, D.. (2022). ex vivo–in vivo comparison of drug penetration analysis by confocal Raman microspectroscopy and tape stripping. in Experimental Dermatology
John Wiley and Sons Inc., 31(12).
https://doi.org/10.1111/exd.14672

Krombholz R, Fressle S, Nikolić I, Pantelić I, Savić S, Crevar-Sakač M, Lunter D. ex vivo–in vivo comparison of drug penetration analysis by confocal Raman microspectroscopy and tape stripping. in Experimental Dermatology. 2022;31(12).
doi:10.1111/exd.14672 .

Krombholz, Richard, Fressle, Stefanie, Nikolić, Ines, Pantelić, Ivana, Savić, Snežana, Crevar-Sakač, Milkica, Lunter, Dominique, "ex vivo–in vivo comparison of drug penetration analysis by confocal Raman microspectroscopy and tape stripping" in Experimental Dermatology, 31, no. 12 (2022),
https://doi.org/10.1111/exd.14672 . .

TY  - JOUR
AU  - Džudović, Jelena
AU  - Crevar-Sakač, Milkica
AU  - Antunović, Marko
AU  - Repić, Aleksandra
AU  - Obradović, Slobodan
AU  - Đorđević, Snežana
AU  - Savić, Jelena
AU  - Džudović, Boris
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4332
AB  - Oral anticoagulants are a group of drugs used for the prevention and treatment of venous thrombosis and venous thromboembolism. For the last ten years, direct oral anticoagulants (DOAC) have been available and are equally effective, but significantly safer than vitamin K antagonists. In the case of an overdose, their most important side effect is still bleeding. Due to their widespread use, as well as increased toxicological importance there is a need to develop an analytical method for the determination of DOAC in biological material. The aim of this paper was to establish a method for the quantification of apixaban as one of the representatives of DOAC. The methodology of the study included the measurement of apixaban in the plasma of patients treated in the intensive care unit. Plasma apixaban concentrations were determined by LC-MS/MS technique using carbamazepine as an internal standard. Obtained validation parameters indicate that the introduced method is sensitive, reliable, precise and accurate. Using this method, apixaban can be quickly and easily detected and quantified in plasma in patients who are suspected of overdosing with this drug.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - Development and validation of LC-MS/MS method for determination of plasma apixaban
VL  - 34
IS  - 3
SP  - 332
EP  - 337
DO  - 10.1556/1326.2021.00948
ER  - 

@article{
author = "Džudović, Jelena and Crevar-Sakač, Milkica and Antunović, Marko and Repić, Aleksandra and Obradović, Slobodan and Đorđević, Snežana and Savić, Jelena and Džudović, Boris",
year = "2022",
abstract = "Oral anticoagulants are a group of drugs used for the prevention and treatment of venous thrombosis and venous thromboembolism. For the last ten years, direct oral anticoagulants (DOAC) have been available and are equally effective, but significantly safer than vitamin K antagonists. In the case of an overdose, their most important side effect is still bleeding. Due to their widespread use, as well as increased toxicological importance there is a need to develop an analytical method for the determination of DOAC in biological material. The aim of this paper was to establish a method for the quantification of apixaban as one of the representatives of DOAC. The methodology of the study included the measurement of apixaban in the plasma of patients treated in the intensive care unit. Plasma apixaban concentrations were determined by LC-MS/MS technique using carbamazepine as an internal standard. Obtained validation parameters indicate that the introduced method is sensitive, reliable, precise and accurate. Using this method, apixaban can be quickly and easily detected and quantified in plasma in patients who are suspected of overdosing with this drug.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "Development and validation of LC-MS/MS method for determination of plasma apixaban",
volume = "34",
number = "3",
pages = "332-337",
doi = "10.1556/1326.2021.00948"
}

Džudović, J., Crevar-Sakač, M., Antunović, M., Repić, A., Obradović, S., Đorđević, S., Savić, J.,& Džudović, B.. (2022). Development and validation of LC-MS/MS method for determination of plasma apixaban. in Acta Chromatographica
Akademiai Kiado ZRt.., 34(3), 332-337.
https://doi.org/10.1556/1326.2021.00948

Džudović J, Crevar-Sakač M, Antunović M, Repić A, Obradović S, Đorđević S, Savić J, Džudović B. Development and validation of LC-MS/MS method for determination of plasma apixaban. in Acta Chromatographica. 2022;34(3):332-337.
doi:10.1556/1326.2021.00948 .

Džudović, Jelena, Crevar-Sakač, Milkica, Antunović, Marko, Repić, Aleksandra, Obradović, Slobodan, Đorđević, Snežana, Savić, Jelena, Džudović, Boris, "Development and validation of LC-MS/MS method for determination of plasma apixaban" in Acta Chromatographica, 34, no. 3 (2022):332-337,
https://doi.org/10.1556/1326.2021.00948 . .

TY  - CONF
AU  - Kurćubić, Ivana
AU  - Vajić, Una‐Jovana
AU  - Cvijić, Sandra
AU  - Crevar-Sakač, Milkica
AU  - Ibrić, Svetlana
AU  - Miloradović, Zoran
AU  - Mihailović‐Stanojević, Nevena
AU  - Ivanov, Milan
AU  - Karanović, Danijela
AU  - Jovović, Đurđica
AU  - Đuriš, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4512
AB  - Mucoadhesive buccal films can improve drug absorption by prolonging its retention
time on the buccal mucosa (1). The aim of the study was a comparative assessment of the
hemodynamic effects and pharmacokinetics of propranolol hydrochloride (PROP) after
buccal and oral administration in spontaneously hypertensive rats. Animals were divided
into 3 groups: Group I (control) received 0.5 mL of water with a gastric tube, group II
received an immediate-release 10 mg PROP tablet via gastric tube, and group III received a
mucoadhesive 10 mg PROP buccal film. Systolic (SP) and diastolic blood pressure (DP), and
heart rate (SF) were measured in rats, and pharmacokinetic PROP parameters, Cmax, tmax,
and AUC0 → 24, were calculated by noncompartmental analysis. Mucoadhesive buccal films
showed superior degree of absorption of PROP over immediate-release tablets (AUC0 → 24:
69.64 μgh/ml versus 24.61 μgh/ml). The tmax value was significantly higher in
mucoadhesive buccal films, which indicates a prolonged PROP release and longer
therapeutic effect (71.19h versus 29.73h). There was no statistically significant difference in
Cmax values between groups II and III of rats (4.74 μg ml versus 7.11 μg ml). Mucoadhesive
buccal films provide a more pronounced and long-lasting reduction primarily of SF
(reduction of 28-51% lasting from 10 minutes to the twelfth hour of testing), but also SP and
DP (between 15-30% from the first to the sixth hour of testing) compared to immediate-
release tablets. Mucoadhesive buccal films allow bypass/reduction of the extensive hepatic
first-pass metabolism, and consequently improve the therapeutic PROP effect.
AB  - Mukoadhezivni bukalni filmovi mogu poboljšati apsorpciju lekovite supstance
produžavajuć i vreme zadržavanja lekovitog preparata na bukalnoj sluznici (1). Cilj studije je
bila komparativna procena hemodinamskih efekata i farmakokinetike propranolol-
hidrohlorida (PROP) nakon bukalne i peroralne primene kod sponatano hipertenzivnih
pacova. Spontano hipertenzivni pacovi su podeljeni u 3 grupe: I (kontrolna) grupa je dobila
0,5 mL vode gastričnom sondom, II grupa je dobila tabletu sa trenutnim oslobađanjem sa 10
mg PROP gastričnom sondom i III grupa je dobila mukoadhezivni bukalni film sa 10 mg
PROP. Filmovi su pripremljeni korišćenjem polietilenoksida, hidroksipropilmetilceluloze i
polivinilalkohola kao film-formirajućih polimera sa mukoadhezivnim svojstvima. Pacovima
su mereni sistolni (SP) i dijastolni krvni pritisak (DP), srčana frekvencija (SF), a
neprostornom farmakokinetičkom analizom izračunati su parametri PROP: Cmax, t max i
AUC0→24 . Mukoadhezivni bukalni filmovi su pokazali superiornost u odnosu na tablete sa
trenutnim oslobađanjem u pogledu stepena apsorpcije PROP (AUC 0→24 : 69,64 μgh/ml
naspram 24,61 μgh/ml). Tmax vrednost je bila značajno veća kod mukoadhezivnih bukalnih
filmova što ukazuje na produženo oslobađanje PROP i duži terapijski efekat (71,19 h
naspram 29,73 h). Između II i II grupe pacova nema statistički značajne razlike u
vrednostima Cmax (4,74 μg/ml naspram 7,11 μg/ml). Mukoadhezivni bukalni filmovi izazivaju
izraženije i dugotrajnije smanjenje pre svega SF (smanjenje od 28-51% u trajanju od 10
minuta do dvanaestog sata ispitivanja), ali i SP i DP (između 15-30% od prvog do šestog sata
ispitivanja) u odnosu na tablete sa trenutnim oslobađanjem. Pripremljeni mukoadhezivni
bukalni filmovi omogućavaju zaobilazak/smanjenje ekstenzivnog metabolizma prvog
prolaza kroz jetru i posledično poboljšavaju terapijski efekat PROP.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension
T1  - Efekti akutne primene mukoadhezivnih bukalnih filmova sa propranolol‐hidrohloridom u animalnom modelu esencijalne hipertenzije
VL  - 72
IS  - 4 suplement
SP  - S235
EP  - S236
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4512
ER  - 

@conference{
author = "Kurćubić, Ivana and Vajić, Una‐Jovana and Cvijić, Sandra and Crevar-Sakač, Milkica and Ibrić, Svetlana and Miloradović, Zoran and Mihailović‐Stanojević, Nevena and Ivanov, Milan and Karanović, Danijela and Jovović, Đurđica and Đuriš, Jelena",
year = "2022",
abstract = "Mucoadhesive buccal films can improve drug absorption by prolonging its retention
time on the buccal mucosa (1). The aim of the study was a comparative assessment of the
hemodynamic effects and pharmacokinetics of propranolol hydrochloride (PROP) after
buccal and oral administration in spontaneously hypertensive rats. Animals were divided
into 3 groups: Group I (control) received 0.5 mL of water with a gastric tube, group II
received an immediate-release 10 mg PROP tablet via gastric tube, and group III received a
mucoadhesive 10 mg PROP buccal film. Systolic (SP) and diastolic blood pressure (DP), and
heart rate (SF) were measured in rats, and pharmacokinetic PROP parameters, Cmax, tmax,
and AUC0 → 24, were calculated by noncompartmental analysis. Mucoadhesive buccal films
showed superior degree of absorption of PROP over immediate-release tablets (AUC0 → 24:
69.64 μgh/ml versus 24.61 μgh/ml). The tmax value was significantly higher in
mucoadhesive buccal films, which indicates a prolonged PROP release and longer
therapeutic effect (71.19h versus 29.73h). There was no statistically significant difference in
Cmax values between groups II and III of rats (4.74 μg ml versus 7.11 μg ml). Mucoadhesive
buccal films provide a more pronounced and long-lasting reduction primarily of SF
(reduction of 28-51% lasting from 10 minutes to the twelfth hour of testing), but also SP and
DP (between 15-30% from the first to the sixth hour of testing) compared to immediate-
release tablets. Mucoadhesive buccal films allow bypass/reduction of the extensive hepatic
first-pass metabolism, and consequently improve the therapeutic PROP effect., Mukoadhezivni bukalni filmovi mogu poboljšati apsorpciju lekovite supstance
produžavajuć i vreme zadržavanja lekovitog preparata na bukalnoj sluznici (1). Cilj studije je
bila komparativna procena hemodinamskih efekata i farmakokinetike propranolol-
hidrohlorida (PROP) nakon bukalne i peroralne primene kod sponatano hipertenzivnih
pacova. Spontano hipertenzivni pacovi su podeljeni u 3 grupe: I (kontrolna) grupa je dobila
0,5 mL vode gastričnom sondom, II grupa je dobila tabletu sa trenutnim oslobađanjem sa 10
mg PROP gastričnom sondom i III grupa je dobila mukoadhezivni bukalni film sa 10 mg
PROP. Filmovi su pripremljeni korišćenjem polietilenoksida, hidroksipropilmetilceluloze i
polivinilalkohola kao film-formirajućih polimera sa mukoadhezivnim svojstvima. Pacovima
su mereni sistolni (SP) i dijastolni krvni pritisak (DP), srčana frekvencija (SF), a
neprostornom farmakokinetičkom analizom izračunati su parametri PROP: Cmax, t max i
AUC0→24 . Mukoadhezivni bukalni filmovi su pokazali superiornost u odnosu na tablete sa
trenutnim oslobađanjem u pogledu stepena apsorpcije PROP (AUC 0→24 : 69,64 μgh/ml
naspram 24,61 μgh/ml). Tmax vrednost je bila značajno veća kod mukoadhezivnih bukalnih
filmova što ukazuje na produženo oslobađanje PROP i duži terapijski efekat (71,19 h
naspram 29,73 h). Između II i II grupe pacova nema statistički značajne razlike u
vrednostima Cmax (4,74 μg/ml naspram 7,11 μg/ml). Mukoadhezivni bukalni filmovi izazivaju
izraženije i dugotrajnije smanjenje pre svega SF (smanjenje od 28-51% u trajanju od 10
minuta do dvanaestog sata ispitivanja), ali i SP i DP (između 15-30% od prvog do šestog sata
ispitivanja) u odnosu na tablete sa trenutnim oslobađanjem. Pripremljeni mukoadhezivni
bukalni filmovi omogućavaju zaobilazak/smanjenje ekstenzivnog metabolizma prvog
prolaza kroz jetru i posledično poboljšavaju terapijski efekat PROP.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension, Efekti akutne primene mukoadhezivnih bukalnih filmova sa propranolol‐hidrohloridom u animalnom modelu esencijalne hipertenzije",
volume = "72",
number = "4 suplement",
pages = "S235-S236",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4512"
}

Kurćubić, I., Vajić, U., Cvijić, S., Crevar-Sakač, M., Ibrić, S., Miloradović, Z., Mihailović‐Stanojević, N., Ivanov, M., Karanović, D., Jovović, Đ.,& Đuriš, J.. (2022). Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S235-S236.
https://hdl.handle.net/21.15107/rcub_farfar_4512

Kurćubić I, Vajić U, Cvijić S, Crevar-Sakač M, Ibrić S, Miloradović Z, Mihailović‐Stanojević N, Ivanov M, Karanović D, Jovović Đ, Đuriš J. Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension. in Arhiv za farmaciju. 2022;72(4 suplement):S235-S236.
https://hdl.handle.net/21.15107/rcub_farfar_4512 .

Kurćubić, Ivana, Vajić, Una‐Jovana, Cvijić, Sandra, Crevar-Sakač, Milkica, Ibrić, Svetlana, Miloradović, Zoran, Mihailović‐Stanojević, Nevena, Ivanov, Milan, Karanović, Danijela, Jovović, Đurđica, Đuriš, Jelena, "Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S235-S236,
https://hdl.handle.net/21.15107/rcub_farfar_4512 .

TY  - JOUR
AU  - Ivković, Branka
AU  - Opačić, Dragan
AU  - Džudović, Boris
AU  - Crevar, Milkica
AU  - Gojković-Bukarica, Ljiljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4306
AB  - It is well known that the presence of different chemical groups in drug molecules influences their pharmacological properties. The aim of our study is to investigate whether newly synthesized derivatives of propafenone, with changes in benzyl moiety, have a different effect upon arrhythmia, compared to propafenone. 5OCl-PF and 5OF-PF are derivatives of propafenone with-Cl or –F substituent on the ortho position of the benzyl moiety. For verification of their antiarrhythmic effect, we used an in vivo rat model of aconitine-induced arrhythmia. 5OCl-PF speeded the appearance of supraventricular premature beats (SVPB) and death more than aconitine. All animals treated with 5OCl-PF developed ventricular premature beats in salvos (VPBS), bigeminies (VPBB) and paroxysmal ventricular tachycardia (PVT). 5OF-PF had a negative chronotropic effect and potentiated atrial excitability (more SVPB). It had a positive effect on the occurrence and onset time of supraventricular tachycardia, VPBS, and PVT. Based on the obtained results, it can be concluded that newly synthesized propafenone derivatives have no better antiarrhythmic effect than the parent compound. In the future, our research will be focused on the synthesis of different derivatives and examining their antiarrhythmic effects.
AB  - Dobro je poznato da prisustvo različitih hemijskih grupa u molekulima leka utiče na
njegova farmakološka svojstva. Cilj našeg istraživanja je ispitati da li novosintetisani derivati
propafenona, s promenama u benzilnoj grupi, imaju drugačiji efekat na aritmiju u odnosu na
propafenon. 5OCl-PF i 5OF-PF su derivati propafenona sa -Cl ili –F supstituentom na orto
položaju benzilnog dela. Za proveru njihovog antiaritmičnog efekta koristili smo in vivo model
na pacovima sa aritmijom izazvanom akonitinom. 5OCl-PF je ubrzao pojavu
supraventrikularnih prevremenih otkucaja (SVPB) i smrt više nego akonitin. Sve životinje
lečene sa 5OCl-PF razvile su ventrikularne prevremene otkucaje (VPBS i VPBB) i
paroksizmalnu ventrikularnu tahikardiju (PVT). 5OF-PF je imao negativan hronotropni efekat i
potencirao atrijalnu ekscitabilnost (više SVPB). Pozitivno je uticao na pojavu i vreme početka
supraventrikularne tahikardije, VPBS i PVT. Na osnovu dobijenih rezultata se može zaključiti
da novosintetisani derivati propafenona nemaju bolji antiaritmijski efekat od polaznog
jedinjenja. U budućnosti, istraživanje će biti usmereno ka sintezi hemijski drugačijih derivata i
ispitivanju njihovog antiaritmijskog efekta.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Antiarrhythmic effects of newly developed propafenone derivatives
T1  - Antiaritmički efekti novosintetisanih derivata
propafenona
VL  - 72
IS  - 4
SP  - 392
EP  - 412
DO  - 10.5937/arhfarm72-37114
ER  - 

@article{
author = "Ivković, Branka and Opačić, Dragan and Džudović, Boris and Crevar, Milkica and Gojković-Bukarica, Ljiljana",
year = "2022",
abstract = "It is well known that the presence of different chemical groups in drug molecules influences their pharmacological properties. The aim of our study is to investigate whether newly synthesized derivatives of propafenone, with changes in benzyl moiety, have a different effect upon arrhythmia, compared to propafenone. 5OCl-PF and 5OF-PF are derivatives of propafenone with-Cl or –F substituent on the ortho position of the benzyl moiety. For verification of their antiarrhythmic effect, we used an in vivo rat model of aconitine-induced arrhythmia. 5OCl-PF speeded the appearance of supraventricular premature beats (SVPB) and death more than aconitine. All animals treated with 5OCl-PF developed ventricular premature beats in salvos (VPBS), bigeminies (VPBB) and paroxysmal ventricular tachycardia (PVT). 5OF-PF had a negative chronotropic effect and potentiated atrial excitability (more SVPB). It had a positive effect on the occurrence and onset time of supraventricular tachycardia, VPBS, and PVT. Based on the obtained results, it can be concluded that newly synthesized propafenone derivatives have no better antiarrhythmic effect than the parent compound. In the future, our research will be focused on the synthesis of different derivatives and examining their antiarrhythmic effects., Dobro je poznato da prisustvo različitih hemijskih grupa u molekulima leka utiče na
njegova farmakološka svojstva. Cilj našeg istraživanja je ispitati da li novosintetisani derivati
propafenona, s promenama u benzilnoj grupi, imaju drugačiji efekat na aritmiju u odnosu na
propafenon. 5OCl-PF i 5OF-PF su derivati propafenona sa -Cl ili –F supstituentom na orto
položaju benzilnog dela. Za proveru njihovog antiaritmičnog efekta koristili smo in vivo model
na pacovima sa aritmijom izazvanom akonitinom. 5OCl-PF je ubrzao pojavu
supraventrikularnih prevremenih otkucaja (SVPB) i smrt više nego akonitin. Sve životinje
lečene sa 5OCl-PF razvile su ventrikularne prevremene otkucaje (VPBS i VPBB) i
paroksizmalnu ventrikularnu tahikardiju (PVT). 5OF-PF je imao negativan hronotropni efekat i
potencirao atrijalnu ekscitabilnost (više SVPB). Pozitivno je uticao na pojavu i vreme početka
supraventrikularne tahikardije, VPBS i PVT. Na osnovu dobijenih rezultata se može zaključiti
da novosintetisani derivati propafenona nemaju bolji antiaritmijski efekat od polaznog
jedinjenja. U budućnosti, istraživanje će biti usmereno ka sintezi hemijski drugačijih derivata i
ispitivanju njihovog antiaritmijskog efekta.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Antiarrhythmic effects of newly developed propafenone derivatives, Antiaritmički efekti novosintetisanih derivata
propafenona",
volume = "72",
number = "4",
pages = "392-412",
doi = "10.5937/arhfarm72-37114"
}

Ivković, B., Opačić, D., Džudović, B., Crevar, M.,& Gojković-Bukarica, L.. (2022). Antiarrhythmic effects of newly developed propafenone derivatives. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(4), 392-412.
https://doi.org/10.5937/arhfarm72-37114

Ivković B, Opačić D, Džudović B, Crevar M, Gojković-Bukarica L. Antiarrhythmic effects of newly developed propafenone derivatives. in Arhiv za farmaciju. 2022;72(4):392-412.
doi:10.5937/arhfarm72-37114 .

Ivković, Branka, Opačić, Dragan, Džudović, Boris, Crevar, Milkica, Gojković-Bukarica, Ljiljana, "Antiarrhythmic effects of newly developed propafenone derivatives" in Arhiv za farmaciju, 72, no. 4 (2022):392-412,
https://doi.org/10.5937/arhfarm72-37114 . .

TY  - JOUR
AU  - Kurćubić, Ivana
AU  - Vajić, Una-Jovana
AU  - Cvijić, Sandra
AU  - Crevar-Sakač, Milkica
AU  - Bogavac-Stanojević, Nataša
AU  - Miloradović, Zoran
AU  - Mihajlović-Stanojević, Nevena
AU  - Ivanov, Milan
AU  - Karanović, Danijela
AU  - Jovović, Đurđica
AU  - Đuriš, Jelena
PY  - 2021
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3990
AB  - The objective of this study was to formulate extended-release mucoadhesive buccal tablets of propranolol hydrochloride in order to provide a prolonged absorption of propranolol hydrochloride from the buccal mucosa and to reduce presystemic metabolism and thus provide a better therapeutic effect. Besides, the aim was to perform comparative in vivo pharmacokinetic and hemodynamic studies of the developed extended-release (ER) propranolol hydrochloride 10 mg mucoadhesive buccal tablets and commercial immediate-release (IR) propranolol hydrochloride 10 mg tablets in spontaneously hypertensive rats. Formulation with 15% polyethylene oxide showed the highest degree of propranolol hydrochloride permeation, satisfactory mucoadhesiveness, and extended-release of propranolol hydrochloride, thus it was selected for further in vivo study. The pharmacokinetic study in rats showed the superiority of ER mucoadhesive buccal tablets over IR tablets in terms of propranolol hydrochloride absorption extent (AUC values: 70.32 ± 19.56 versus 31.69 ± 6.97 μg⋅h/mL), although lower maximum plasma propranolol hydrochloride concentration (Cmax) was achieved. However, no statistically significant difference was observed in Cmax between these treatments. The hemodynamic study showed that ER mucoadhesive buccal tablets provide a more pronounced decrease primarily in heart rate, but also in systolic and diastolic arterial pressure, as well as a longer heart rate reduction compared to IR tablets.
PB  - Elsevier B.V.
T2  - International Journal of Pharmaceutics
T1  - Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension
VL  - 610
DO  - 10.1016/j.ijpharm.2021.121266
ER  - 

@article{
author = "Kurćubić, Ivana and Vajić, Una-Jovana and Cvijić, Sandra and Crevar-Sakač, Milkica and Bogavac-Stanojević, Nataša and Miloradović, Zoran and Mihajlović-Stanojević, Nevena and Ivanov, Milan and Karanović, Danijela and Jovović, Đurđica and Đuriš, Jelena",
year = "2021, 2021",
abstract = "The objective of this study was to formulate extended-release mucoadhesive buccal tablets of propranolol hydrochloride in order to provide a prolonged absorption of propranolol hydrochloride from the buccal mucosa and to reduce presystemic metabolism and thus provide a better therapeutic effect. Besides, the aim was to perform comparative in vivo pharmacokinetic and hemodynamic studies of the developed extended-release (ER) propranolol hydrochloride 10 mg mucoadhesive buccal tablets and commercial immediate-release (IR) propranolol hydrochloride 10 mg tablets in spontaneously hypertensive rats. Formulation with 15% polyethylene oxide showed the highest degree of propranolol hydrochloride permeation, satisfactory mucoadhesiveness, and extended-release of propranolol hydrochloride, thus it was selected for further in vivo study. The pharmacokinetic study in rats showed the superiority of ER mucoadhesive buccal tablets over IR tablets in terms of propranolol hydrochloride absorption extent (AUC values: 70.32 ± 19.56 versus 31.69 ± 6.97 μg⋅h/mL), although lower maximum plasma propranolol hydrochloride concentration (Cmax) was achieved. However, no statistically significant difference was observed in Cmax between these treatments. The hemodynamic study showed that ER mucoadhesive buccal tablets provide a more pronounced decrease primarily in heart rate, but also in systolic and diastolic arterial pressure, as well as a longer heart rate reduction compared to IR tablets.",
publisher = "Elsevier B.V.",
journal = "International Journal of Pharmaceutics",
title = "Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension",
volume = "610",
doi = "10.1016/j.ijpharm.2021.121266"
}

Kurćubić, I., Vajić, U., Cvijić, S., Crevar-Sakač, M., Bogavac-Stanojević, N., Miloradović, Z., Mihajlović-Stanojević, N., Ivanov, M., Karanović, D., Jovović, Đ.,& Đuriš, J.. (2021). Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension. in International Journal of Pharmaceutics
Elsevier B.V.., 610.
https://doi.org/10.1016/j.ijpharm.2021.121266

Kurćubić I, Vajić U, Cvijić S, Crevar-Sakač M, Bogavac-Stanojević N, Miloradović Z, Mihajlović-Stanojević N, Ivanov M, Karanović D, Jovović Đ, Đuriš J. Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension. in International Journal of Pharmaceutics. 2021;610.
doi:10.1016/j.ijpharm.2021.121266 .

Kurćubić, Ivana, Vajić, Una-Jovana, Cvijić, Sandra, Crevar-Sakač, Milkica, Bogavac-Stanojević, Nataša, Miloradović, Zoran, Mihajlović-Stanojević, Nevena, Ivanov, Milan, Karanović, Danijela, Jovović, Đurđica, Đuriš, Jelena, "Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension" in International Journal of Pharmaceutics, 610 (2021),
https://doi.org/10.1016/j.ijpharm.2021.121266 . .

TY  - JOUR
AU  - Odović, Jadranka
AU  - Crevar-Sakač, Milkica
AU  - Vujić, Zorica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3713
AB  - Antifungal agents are the group of drugs commonly prescribed in the treatment  of  fungal  infections,  which  are  widely  spread  among  the  global population.  Their  properties,  such  as  absorption,  distribution,  metabolism, route of elimination or plasma protein binding (PPB), considerably influence their  therapeutic  success,  while  a  number  of  the  molecular  physicochemical properties  of  the  drug  notably  influence  all  these  processes.  Lipophilicity (log P), molecular weight (Mw), volume (Vol), polar surface area (PSA) and solubility (log S) play important roles in drug absorption, penetration into tis-sues, distribution and route of elimination or the degree of plasma protein bind-ing. In this study, the relationships between these five molecular properties of eight  antifungal  drugs  and  their  plasma  protein  binding  data  obtained  from relevant literature were investigated. The Selected physicochemical molecular descriptors of the drug were calculated using software packages. The estab-lished relationships between PPB and PSA; Mw; Vol and log S were showed relatively poor correlation (r < 0.35). The best correlation was obtained for the relationship  between PPB  data  and  the  lipophilicity  descriptor X  log P3 (correlation coefficient r = 0.55). In further investigation, multiple linear reg-ression analysis was applied. The best correlation was obtained with applicat-ion of lipophilicity with polar surface area (r = 0.918) and volume (r = 0.916) or molecular weight (r = 0.896) as independent variables.
AB  - Антифунгалнасредствапредстављајугрупулековакојисепримењујуулечењугљи-вичнихинфекција, данасширокораспрострањенихмеђуглобалномпопулацијом. Одњиховихособинакаоштосуапсорпција, дистрибуција, метаболизам, путелиминацијеиливезивањезапротеинеплазмe значајнозависињиховтерапеутскиуспех, абројнефизичко–хемијскеособинемолекулалекаутичунасвеовепроцесе. Липофилност(log P), молекулскамаса (Mw), запремина (Vol), поларнаповршина (PSA) ираствор-љивост (log S) играјуважнуулогууапсорпцијилека, продирањууткива, дистрибуцији, путуелиминацијеилистепенувезивањазапротеинеплазме. Уовомрадузаосаманти-фунгалнихлековаистраженисуодносиизмеђуособинамолекулаистепенањиховогвезивањазапротеинеплазме (PPB). Дескрипторифизичко–хемијскихособинамолекулаиспитиванихантифунгалнихлековаизрачунатисупомоћуодабранихсофтверскихпакета, доксуподациоњиховомPPBприкупљениизодговарајућелитературе. ОдносиизмеђуPPBиPSA, Mw, Volи  log Sпоказалисулошукорелацију (r < 0,35) докјебољакорелацијадобијенајеизмеђуподатакаоPPBидеск  рипторалипофилности, X log  P3вредности (r = 0,55). Удаљемиспитивању, примењенајевишеструкалинеарнарегре-сионаанализа. НајбољезависностидобијенесуизмеђуPPBвредностиилипофилностиузприменуполарнеповршинемолекула (r = 0,918), волумена (r = 0,916) имолекулскемасе (r = 0,896) каонезависнопроменљивих.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - The correlation of plasma protein binding and molecular properties of selected antifungal drugs
T1  - КОРЕЛАЦИЈАСТЕПЕНАВЕЗИВАЊАЗАПРОТЕИНЕПЛАЗМЕИОСОБИНАМОЛЕКУЛАОДАБРАНИХАНТИФУНГАЛНИХЛЕКОВА
VL  - 85
IS  - 7
SP  - 897
EP  - 907
DO  - 10.2298/JSC190925125O
DO  - 2-s2.0-85092602809
ER  - 

@article{
author = "Odović, Jadranka and Crevar-Sakač, Milkica and Vujić, Zorica",
year = "2020",
abstract = "Antifungal agents are the group of drugs commonly prescribed in the treatment  of  fungal  infections,  which  are  widely  spread  among  the  global population.  Their  properties,  such  as  absorption,  distribution,  metabolism, route of elimination or plasma protein binding (PPB), considerably influence their  therapeutic  success,  while  a  number  of  the  molecular  physicochemical properties  of  the  drug  notably  influence  all  these  processes.  Lipophilicity (log P), molecular weight (Mw), volume (Vol), polar surface area (PSA) and solubility (log S) play important roles in drug absorption, penetration into tis-sues, distribution and route of elimination or the degree of plasma protein bind-ing. In this study, the relationships between these five molecular properties of eight  antifungal  drugs  and  their  plasma  protein  binding  data  obtained  from relevant literature were investigated. The Selected physicochemical molecular descriptors of the drug were calculated using software packages. The estab-lished relationships between PPB and PSA; Mw; Vol and log S were showed relatively poor correlation (r < 0.35). The best correlation was obtained for the relationship  between PPB  data  and  the  lipophilicity  descriptor X  log P3 (correlation coefficient r = 0.55). In further investigation, multiple linear reg-ression analysis was applied. The best correlation was obtained with applicat-ion of lipophilicity with polar surface area (r = 0.918) and volume (r = 0.916) or molecular weight (r = 0.896) as independent variables., Антифунгалнасредствапредстављајугрупулековакојисепримењујуулечењугљи-вичнихинфекција, данасширокораспрострањенихмеђуглобалномпопулацијом. Одњиховихособинакаоштосуапсорпција, дистрибуција, метаболизам, путелиминацијеиливезивањезапротеинеплазмe значајнозависињиховтерапеутскиуспех, абројнефизичко–хемијскеособинемолекулалекаутичунасвеовепроцесе. Липофилност(log P), молекулскамаса (Mw), запремина (Vol), поларнаповршина (PSA) ираствор-љивост (log S) играјуважнуулогууапсорпцијилека, продирањууткива, дистрибуцији, путуелиминацијеилистепенувезивањазапротеинеплазме. Уовомрадузаосаманти-фунгалнихлековаистраженисуодносиизмеђуособинамолекулаистепенањиховогвезивањазапротеинеплазме (PPB). Дескрипторифизичко–хемијскихособинамолекулаиспитиванихантифунгалнихлековаизрачунатисупомоћуодабранихсофтверскихпакета, доксуподациоњиховомPPBприкупљениизодговарајућелитературе. ОдносиизмеђуPPBиPSA, Mw, Volи  log Sпоказалисулошукорелацију (r < 0,35) докјебољакорелацијадобијенајеизмеђуподатакаоPPBидеск  рипторалипофилности, X log  P3вредности (r = 0,55). Удаљемиспитивању, примењенајевишеструкалинеарнарегре-сионаанализа. НајбољезависностидобијенесуизмеђуPPBвредностиилипофилностиузприменуполарнеповршинемолекула (r = 0,918), волумена (r = 0,916) имолекулскемасе (r = 0,896) каонезависнопроменљивих.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "The correlation of plasma protein binding and molecular properties of selected antifungal drugs, КОРЕЛАЦИЈАСТЕПЕНАВЕЗИВАЊАЗАПРОТЕИНЕПЛАЗМЕИОСОБИНАМОЛЕКУЛАОДАБРАНИХАНТИФУНГАЛНИХЛЕКОВА",
volume = "85",
number = "7",
pages = "897-907",
doi = "10.2298/JSC190925125O, 2-s2.0-85092602809"
}

Odović, J., Crevar-Sakač, M.,& Vujić, Z.. (2020). The correlation of plasma protein binding and molecular properties of selected antifungal drugs. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 85(7), 897-907.
https://doi.org/10.2298/JSC190925125O

Odović J, Crevar-Sakač M, Vujić Z. The correlation of plasma protein binding and molecular properties of selected antifungal drugs. in Journal of the Serbian Chemical Society. 2020;85(7):897-907.
doi:10.2298/JSC190925125O .

Odović, Jadranka, Crevar-Sakač, Milkica, Vujić, Zorica, "The correlation of plasma protein binding and molecular properties of selected antifungal drugs" in Journal of the Serbian Chemical Society, 85, no. 7 (2020):897-907,
https://doi.org/10.2298/JSC190925125O . .

TY  - JOUR
AU  - Stevanović, Milena
AU  - Đošić, Marija
AU  - Janković, Ana
AU  - Kojić, Vesna
AU  - Vukašinović-Sekulić, Maja
AU  - Stojanović, Jovica
AU  - Odović, Jadranka
AU  - Crevar-Sakač, Milkica
AU  - Kyong Yop, Rhee
AU  - Mišković-Stanković, Vesna
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3657
AB  - Electrophoretic deposition process (EPD) was successfully used for obtaining graphene (Gr)-reinforced composite coating based on hydroxyapatite (HAP), chitosan (CS), and antibiotic gentamicin (Gent), from aqueous suspension. The deposition process was performed as a single step process at a constant voltage (5 V, deposition time 12 min) on pure titanium foils. The influence of graphene was examined through detailed physicochemical and biological characterization. Fourier transform infrared spectroscopy, field emission scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, Raman, and X-ray photoelectron analyses confirmed the formation of composite HAP/CS/Gr and HAP/CS/Gr/Gent coatings on Ti. Obtained coatings had porous, uniform, fracture-free surfaces, suggesting strong interfacial interaction between HAP, CS, and Gr. Large specific area of graphene enabled strong bonding with chitosan, acting as nanofiller throughout the polymer matrix. Gentamicin addition strongly improved the antibacterial activity of HAP/CS/Gr/Gent coating that was confirmed by antibacterial activity kinetics in suspension and agar diffusion testing, while results indicated more pronounced antibacterial effect against Staphylococcus aureus (bactericidal, viable cells number reduction >3 logarithmic units) compared to Escherichia coli (bacteriostatic, <3 logarithmic units). MTT assay indicated low cytotoxicity (75% cell viability) against MRC-5 and L929 (70% cell viability) tested cell lines, indicating good biocompatibility of HAP/CS/Gr/Gent coating. Therefore, electrodeposited HAP/CS/Gr/Gent coating on Ti can be considered as a prospective material for bone tissue engineering as a hard tissue implant.
PB  - Wiley Periodicals, LLC.
T2  - Journal of Biomedical Materials Research - Part A
T1  - Antibacterial graphene-based hydroxyapatite/chitosan coating with gentamicin for potential applications in bone tissue engineering
VL  - 108
IS  - 11
SP  - 2175
EP  - 2189
DO  - 10.1002/jbm.a.36974
ER  - 

@article{
author = "Stevanović, Milena and Đošić, Marija and Janković, Ana and Kojić, Vesna and Vukašinović-Sekulić, Maja and Stojanović, Jovica and Odović, Jadranka and Crevar-Sakač, Milkica and Kyong Yop, Rhee and Mišković-Stanković, Vesna",
year = "2020",
abstract = "Electrophoretic deposition process (EPD) was successfully used for obtaining graphene (Gr)-reinforced composite coating based on hydroxyapatite (HAP), chitosan (CS), and antibiotic gentamicin (Gent), from aqueous suspension. The deposition process was performed as a single step process at a constant voltage (5 V, deposition time 12 min) on pure titanium foils. The influence of graphene was examined through detailed physicochemical and biological characterization. Fourier transform infrared spectroscopy, field emission scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, Raman, and X-ray photoelectron analyses confirmed the formation of composite HAP/CS/Gr and HAP/CS/Gr/Gent coatings on Ti. Obtained coatings had porous, uniform, fracture-free surfaces, suggesting strong interfacial interaction between HAP, CS, and Gr. Large specific area of graphene enabled strong bonding with chitosan, acting as nanofiller throughout the polymer matrix. Gentamicin addition strongly improved the antibacterial activity of HAP/CS/Gr/Gent coating that was confirmed by antibacterial activity kinetics in suspension and agar diffusion testing, while results indicated more pronounced antibacterial effect against Staphylococcus aureus (bactericidal, viable cells number reduction >3 logarithmic units) compared to Escherichia coli (bacteriostatic, <3 logarithmic units). MTT assay indicated low cytotoxicity (75% cell viability) against MRC-5 and L929 (70% cell viability) tested cell lines, indicating good biocompatibility of HAP/CS/Gr/Gent coating. Therefore, electrodeposited HAP/CS/Gr/Gent coating on Ti can be considered as a prospective material for bone tissue engineering as a hard tissue implant.",
publisher = "Wiley Periodicals, LLC.",
journal = "Journal of Biomedical Materials Research - Part A",
title = "Antibacterial graphene-based hydroxyapatite/chitosan coating with gentamicin for potential applications in bone tissue engineering",
volume = "108",
number = "11",
pages = "2175-2189",
doi = "10.1002/jbm.a.36974"
}

Stevanović, M., Đošić, M., Janković, A., Kojić, V., Vukašinović-Sekulić, M., Stojanović, J., Odović, J., Crevar-Sakač, M., Kyong Yop, R.,& Mišković-Stanković, V.. (2020). Antibacterial graphene-based hydroxyapatite/chitosan coating with gentamicin for potential applications in bone tissue engineering. in Journal of Biomedical Materials Research - Part A
Wiley Periodicals, LLC.., 108(11), 2175-2189.
https://doi.org/10.1002/jbm.a.36974

Stevanović M, Đošić M, Janković A, Kojić V, Vukašinović-Sekulić M, Stojanović J, Odović J, Crevar-Sakač M, Kyong Yop R, Mišković-Stanković V. Antibacterial graphene-based hydroxyapatite/chitosan coating with gentamicin for potential applications in bone tissue engineering. in Journal of Biomedical Materials Research - Part A. 2020;108(11):2175-2189.
doi:10.1002/jbm.a.36974 .

Stevanović, Milena, Đošić, Marija, Janković, Ana, Kojić, Vesna, Vukašinović-Sekulić, Maja, Stojanović, Jovica, Odović, Jadranka, Crevar-Sakač, Milkica, Kyong Yop, Rhee, Mišković-Stanković, Vesna, "Antibacterial graphene-based hydroxyapatite/chitosan coating with gentamicin for potential applications in bone tissue engineering" in Journal of Biomedical Materials Research - Part A, 108, no. 11 (2020):2175-2189,
https://doi.org/10.1002/jbm.a.36974 . .

TY  - JOUR
AU  - Savić, Jelena
AU  - Dilber, Sanda
AU  - Crevar-Sakač, Milkica
AU  - Vladimirov, Sote
AU  - Brborić, Jasmina
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3096
AB  - Lipophilicity parameters (logP) were determined for thirteen synthesized β-hydroxy-β-arilalkanoic acids using reversed phase high performance liquid chromatography. Anti-inflammatory activity and potential selectivity towards cyclooxygenase-2 inhibition of synthetized compounds was assessed. Stationary phase was octadecyl modified (C-18) silicagel, and four used mobile phases contained different amount of methanol. Both synthetized and standard compounds with known logP values (aspirin, ibuprofen, ketoprofen, naproxen and phenanthrene) were tested in a chromatographic system. Using retention times for each standard and synthesized compound logk values (logarithm of capacity factor) were calculated. Intercept on a graph showing dependency of logk from methanol amount in the mobile phase for each compound represents logKw(capacity factor when organic solvent amount is zero). Graph showing linear dependency of logP of standard compounds from experimentally obtained logKw values was plotted. LogP values for synthetized compounds were obtained by interpolation from the plotted graph. Obtained values are in a range from 2.901 to 3.847. The best correlation between experimentally obtained and predicted logP values was using KOWWIN software (R2=0.8864), which makes this software appropriate for predicting logP values of this type of compounds.
AB  - Parametri lipofilnosti (logP) su određeni za trinaest sintetisanih β-hidroksi-β-arilalkanskih kiselina primenom reverzno fazne tečne hromatografije. Ispitivanje je urađeno na derivatima kojima je tokom prethodnih istraživanja okarakterisana antiinflamatorna aktivnost i pretpostavljena je potencijalna selektivnost prema inhibiciji ciklooksigenaze-2. Oktadecil-modifikovani (C-18) silikagel je predstavljao stacionarnu fazu, a korišćene su četiri mobilne faze u kojima je variran udeo metanola. Hromatografski su testirana jedinjenja sa poznatim logP vrednostima (aspirin, ibuprofen, ketoprofen, naproksen i fenantren) i sintetisana jedinjenja. Na osnovu retencionog vremena za svako standardno i sintetisano jedinjenje izračunate su vrednosti logk (logaritam faktora kapaciteta). Odsečak na y osi grafika zavisnosti logk od udela metanola u mobilnoj fazi za svako jedinjenje predstavlja vrednost logKw (vrednost retencionog faktora za hromatografski sistem u kome je sadržaj organske komponente nula) za dato jedinjenje. Konstruisan je grafik zavisnosti logP za standardna jedinjenja od njihovih eksperimentalno dobijenih logKw vrednosti i uspostavljena je linearna zavisnost. Interpolacijom logKw sa grafika su očitane vrednosti logP za sintetisana jedinjenja. Dobijene vrednosti su u opsegu od 2,901 do 3,847. Za predviđanje logP vrednosti korišćeni su računarski programi: AlogPS, Molinspiration, MarvinSketch i KOWWIN. Najbolja korelacija između eksperimentalno određenih i predviđenih rezultata je u programu KOWWIN (R2=0,8864), što čini ovaj program pogodnim za predviđanje logP vrednosti ovog tipa jedinjenja.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Lipophilicity determination of β-hydroxy-β-arilalkanoic acids by reversed phase liquid chromatography under high pressure
T1  - Određivanje lipofilnosti β-hidroksi-β-arilalkanskih kiselina primenom reverzno-fazne tečne hromatografije pod visokim pritiskom
VL  - 68
IS  - 1
SP  - 34
EP  - 45
DO  - 10.5937/arhFarm1801034S
ER  - 

@article{
author = "Savić, Jelena and Dilber, Sanda and Crevar-Sakač, Milkica and Vladimirov, Sote and Brborić, Jasmina",
year = "2018",
abstract = "Lipophilicity parameters (logP) were determined for thirteen synthesized β-hydroxy-β-arilalkanoic acids using reversed phase high performance liquid chromatography. Anti-inflammatory activity and potential selectivity towards cyclooxygenase-2 inhibition of synthetized compounds was assessed. Stationary phase was octadecyl modified (C-18) silicagel, and four used mobile phases contained different amount of methanol. Both synthetized and standard compounds with known logP values (aspirin, ibuprofen, ketoprofen, naproxen and phenanthrene) were tested in a chromatographic system. Using retention times for each standard and synthesized compound logk values (logarithm of capacity factor) were calculated. Intercept on a graph showing dependency of logk from methanol amount in the mobile phase for each compound represents logKw(capacity factor when organic solvent amount is zero). Graph showing linear dependency of logP of standard compounds from experimentally obtained logKw values was plotted. LogP values for synthetized compounds were obtained by interpolation from the plotted graph. Obtained values are in a range from 2.901 to 3.847. The best correlation between experimentally obtained and predicted logP values was using KOWWIN software (R2=0.8864), which makes this software appropriate for predicting logP values of this type of compounds., Parametri lipofilnosti (logP) su određeni za trinaest sintetisanih β-hidroksi-β-arilalkanskih kiselina primenom reverzno fazne tečne hromatografije. Ispitivanje je urađeno na derivatima kojima je tokom prethodnih istraživanja okarakterisana antiinflamatorna aktivnost i pretpostavljena je potencijalna selektivnost prema inhibiciji ciklooksigenaze-2. Oktadecil-modifikovani (C-18) silikagel je predstavljao stacionarnu fazu, a korišćene su četiri mobilne faze u kojima je variran udeo metanola. Hromatografski su testirana jedinjenja sa poznatim logP vrednostima (aspirin, ibuprofen, ketoprofen, naproksen i fenantren) i sintetisana jedinjenja. Na osnovu retencionog vremena za svako standardno i sintetisano jedinjenje izračunate su vrednosti logk (logaritam faktora kapaciteta). Odsečak na y osi grafika zavisnosti logk od udela metanola u mobilnoj fazi za svako jedinjenje predstavlja vrednost logKw (vrednost retencionog faktora za hromatografski sistem u kome je sadržaj organske komponente nula) za dato jedinjenje. Konstruisan je grafik zavisnosti logP za standardna jedinjenja od njihovih eksperimentalno dobijenih logKw vrednosti i uspostavljena je linearna zavisnost. Interpolacijom logKw sa grafika su očitane vrednosti logP za sintetisana jedinjenja. Dobijene vrednosti su u opsegu od 2,901 do 3,847. Za predviđanje logP vrednosti korišćeni su računarski programi: AlogPS, Molinspiration, MarvinSketch i KOWWIN. Najbolja korelacija između eksperimentalno određenih i predviđenih rezultata je u programu KOWWIN (R2=0,8864), što čini ovaj program pogodnim za predviđanje logP vrednosti ovog tipa jedinjenja.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Lipophilicity determination of β-hydroxy-β-arilalkanoic acids by reversed phase liquid chromatography under high pressure, Određivanje lipofilnosti β-hidroksi-β-arilalkanskih kiselina primenom reverzno-fazne tečne hromatografije pod visokim pritiskom",
volume = "68",
number = "1",
pages = "34-45",
doi = "10.5937/arhFarm1801034S"
}

Savić, J., Dilber, S., Crevar-Sakač, M., Vladimirov, S.,& Brborić, J.. (2018). Lipophilicity determination of β-hydroxy-β-arilalkanoic acids by reversed phase liquid chromatography under high pressure. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 68(1), 34-45.
https://doi.org/10.5937/arhFarm1801034S

Savić J, Dilber S, Crevar-Sakač M, Vladimirov S, Brborić J. Lipophilicity determination of β-hydroxy-β-arilalkanoic acids by reversed phase liquid chromatography under high pressure. in Arhiv za farmaciju. 2018;68(1):34-45.
doi:10.5937/arhFarm1801034S .

Savić, Jelena, Dilber, Sanda, Crevar-Sakač, Milkica, Vladimirov, Sote, Brborić, Jasmina, "Lipophilicity determination of β-hydroxy-β-arilalkanoic acids by reversed phase liquid chromatography under high pressure" in Arhiv za farmaciju, 68, no. 1 (2018):34-45,
https://doi.org/10.5937/arhFarm1801034S . .

TY  - JOUR
AU  - Bogavac-Stanojević, Nataša
AU  - Kotur-Stevuljević, Jelena
AU  - Cerne, Darko
AU  - Zupan, Janja
AU  - Marc, Janja
AU  - Vujić, Zorica
AU  - Crevar-Sakač, Milkica
AU  - Sopić, Miron
AU  - Munjas, Jelena
AU  - Radenković, Miroslav
AU  - Jelić-Ivanović, Zorana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3189
AB  - Context: Polyphenols and flavonoids in artichoke leaf tincture (ALT) protect cells against oxidative damage. Objectives: We examined ALT effects on deoxyribonucleic acid (DNA) damage and lipid profiles in rat plasma and gene expression in rat aorta [haemeoxygenase-1 (HO1), haemeoxygenase-2 (HO2), NADPH oxidase 4 (NOX-4), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. Materials and methods: Eighteen male Wistar albino rats were divided into three groups (n=6/group): The control group (CG) was fed with standard pellet chow for 11 weeks; the AD group was fed for a similar period of time with pellet chow supplemented with 2% cholesterol, 3% sunflower oil and 1% sodium cholate. The ADA group was fed with pellet chow (for 1 week), the atherogenic diet (see above) for the following 4 weeks and then with ALT (0.1 mL/kg body weight) and atherogenic diet for 6 weeks. According to HPLC analysis, the isolated main compounds in ALT were chlorogenic acid, caffeic acid, isoquercitrin and rutin. Results: Normalized HO-1 [0.11 (0.04-0.24)] and MCP-1 [0.29 (0.21-0.47)] mRNA levels and DNA scores [12.50 (4.50-36.50)] were significantly lower in the ADA group than in the AD group [0.84 (0.35-2.51)], p = 0.021 for HO-1 [0.85 (0.61-3.45)], p = 0.047 for MCP-1 and [176.5 (66.50-221.25)], p = 0.020 for DNA scores. HO-1 mRNA was lower in the ADA group than in the CG group [0.30 (0.21-0.71), p = 0.049]. Conclusions: Supplementation with ALT limited the effects of the atherogenic diet through reduced MCP-1 expression, thereby preventing oxidative damage.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Pharmaceutical Biology
T1  - The role of artichoke leaf tincture (Cynara scolymus) in the suppression of DNA damage and atherosclerosis in rats fed an atherogenic diet
VL  - 56
IS  - 1
SP  - 138
EP  - 144
DO  - 10.1080/13880209.2018.1434549
ER  - 

@article{
author = "Bogavac-Stanojević, Nataša and Kotur-Stevuljević, Jelena and Cerne, Darko and Zupan, Janja and Marc, Janja and Vujić, Zorica and Crevar-Sakač, Milkica and Sopić, Miron and Munjas, Jelena and Radenković, Miroslav and Jelić-Ivanović, Zorana",
year = "2018",
abstract = "Context: Polyphenols and flavonoids in artichoke leaf tincture (ALT) protect cells against oxidative damage. Objectives: We examined ALT effects on deoxyribonucleic acid (DNA) damage and lipid profiles in rat plasma and gene expression in rat aorta [haemeoxygenase-1 (HO1), haemeoxygenase-2 (HO2), NADPH oxidase 4 (NOX-4), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. Materials and methods: Eighteen male Wistar albino rats were divided into three groups (n=6/group): The control group (CG) was fed with standard pellet chow for 11 weeks; the AD group was fed for a similar period of time with pellet chow supplemented with 2% cholesterol, 3% sunflower oil and 1% sodium cholate. The ADA group was fed with pellet chow (for 1 week), the atherogenic diet (see above) for the following 4 weeks and then with ALT (0.1 mL/kg body weight) and atherogenic diet for 6 weeks. According to HPLC analysis, the isolated main compounds in ALT were chlorogenic acid, caffeic acid, isoquercitrin and rutin. Results: Normalized HO-1 [0.11 (0.04-0.24)] and MCP-1 [0.29 (0.21-0.47)] mRNA levels and DNA scores [12.50 (4.50-36.50)] were significantly lower in the ADA group than in the AD group [0.84 (0.35-2.51)], p = 0.021 for HO-1 [0.85 (0.61-3.45)], p = 0.047 for MCP-1 and [176.5 (66.50-221.25)], p = 0.020 for DNA scores. HO-1 mRNA was lower in the ADA group than in the CG group [0.30 (0.21-0.71), p = 0.049]. Conclusions: Supplementation with ALT limited the effects of the atherogenic diet through reduced MCP-1 expression, thereby preventing oxidative damage.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Pharmaceutical Biology",
title = "The role of artichoke leaf tincture (Cynara scolymus) in the suppression of DNA damage and atherosclerosis in rats fed an atherogenic diet",
volume = "56",
number = "1",
pages = "138-144",
doi = "10.1080/13880209.2018.1434549"
}

Bogavac-Stanojević, N., Kotur-Stevuljević, J., Cerne, D., Zupan, J., Marc, J., Vujić, Z., Crevar-Sakač, M., Sopić, M., Munjas, J., Radenković, M.,& Jelić-Ivanović, Z.. (2018). The role of artichoke leaf tincture (Cynara scolymus) in the suppression of DNA damage and atherosclerosis in rats fed an atherogenic diet. in Pharmaceutical Biology
Taylor & Francis Ltd, Abingdon., 56(1), 138-144.
https://doi.org/10.1080/13880209.2018.1434549

Bogavac-Stanojević N, Kotur-Stevuljević J, Cerne D, Zupan J, Marc J, Vujić Z, Crevar-Sakač M, Sopić M, Munjas J, Radenković M, Jelić-Ivanović Z. The role of artichoke leaf tincture (Cynara scolymus) in the suppression of DNA damage and atherosclerosis in rats fed an atherogenic diet. in Pharmaceutical Biology. 2018;56(1):138-144.
doi:10.1080/13880209.2018.1434549 .

Bogavac-Stanojević, Nataša, Kotur-Stevuljević, Jelena, Cerne, Darko, Zupan, Janja, Marc, Janja, Vujić, Zorica, Crevar-Sakač, Milkica, Sopić, Miron, Munjas, Jelena, Radenković, Miroslav, Jelić-Ivanović, Zorana, "The role of artichoke leaf tincture (Cynara scolymus) in the suppression of DNA damage and atherosclerosis in rats fed an atherogenic diet" in Pharmaceutical Biology, 56, no. 1 (2018):138-144,
https://doi.org/10.1080/13880209.2018.1434549 . .

TY  - JOUR
AU  - Ninić, Ana
AU  - Spasojević-Kalimanovska, Vesna
AU  - Sopić, Miron
AU  - Munjas, Jelena
AU  - Bogavac-Stanojević, Nataša
AU  - Jelić-Ivanović, Zorana
AU  - Kotur-Stevuljević, Jelena
AU  - Spasić, Slavica
AU  - Crevar-Sakač, Milkica
AU  - Milenković, Marina
AU  - Vujić, Zorica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3054
AB  - Paraoxonases isoenzymes, PON1, PON2 and PON3, have important antioxidative and anti-inflammatory properties in blood and cells. They prevent oxidation of low and high density lipoprotein particles, foam cells formation and development of atherosclerosis. The authors investigated effects of high fat diet and atorvastatin therapy on paraoxonases gene expression levels and distribution in different rat organs. Liver, white adipose tissue (WAT) and aorta were taken from young male Wistar rats that were fed with normal diet (ND), atherogenic diet (AD) and atherogenic diet with 1.14 mg of atorvastatin per kg (ADA). Messenger RNA (mRNA) relative levels of paraoxonase 1 (PON1), paraoxonase 2 (PON2) and paraoxonase 3 (PON3) were measured in rat organs using real-time polymerase chain reaction (PCR). PON1 mRNA expression levels were down-regulated in ADA compared to AD group. ND group had significantly lower PON2 mRNA expression than AD group. PON1 mRNA expression levels were higher in liver than in aorta in group of rats on ND, AD and ADA. PON2 mRNA expression was higher in WAT than in aorta only in ADA group of rats. PON2 and PON3 were significantly higher than PON1 in aorta of rats on each ND, AD or ADA.
PB  - Natl Inst Science Communication-Niscair, New Delhi
T2  - Indian Journal of Biotechnology
T1  - Paraoxonases gene expression and distribution in rats organs treated with atherogenic diet and atorvastatin therapy
VL  - 17
IS  - 2
SP  - 217
EP  - 223
UR  - https://hdl.handle.net/21.15107/rcub_farfar_3054
ER  - 

@article{
author = "Ninić, Ana and Spasojević-Kalimanovska, Vesna and Sopić, Miron and Munjas, Jelena and Bogavac-Stanojević, Nataša and Jelić-Ivanović, Zorana and Kotur-Stevuljević, Jelena and Spasić, Slavica and Crevar-Sakač, Milkica and Milenković, Marina and Vujić, Zorica",
year = "2018",
abstract = "Paraoxonases isoenzymes, PON1, PON2 and PON3, have important antioxidative and anti-inflammatory properties in blood and cells. They prevent oxidation of low and high density lipoprotein particles, foam cells formation and development of atherosclerosis. The authors investigated effects of high fat diet and atorvastatin therapy on paraoxonases gene expression levels and distribution in different rat organs. Liver, white adipose tissue (WAT) and aorta were taken from young male Wistar rats that were fed with normal diet (ND), atherogenic diet (AD) and atherogenic diet with 1.14 mg of atorvastatin per kg (ADA). Messenger RNA (mRNA) relative levels of paraoxonase 1 (PON1), paraoxonase 2 (PON2) and paraoxonase 3 (PON3) were measured in rat organs using real-time polymerase chain reaction (PCR). PON1 mRNA expression levels were down-regulated in ADA compared to AD group. ND group had significantly lower PON2 mRNA expression than AD group. PON1 mRNA expression levels were higher in liver than in aorta in group of rats on ND, AD and ADA. PON2 mRNA expression was higher in WAT than in aorta only in ADA group of rats. PON2 and PON3 were significantly higher than PON1 in aorta of rats on each ND, AD or ADA.",
publisher = "Natl Inst Science Communication-Niscair, New Delhi",
journal = "Indian Journal of Biotechnology",
title = "Paraoxonases gene expression and distribution in rats organs treated with atherogenic diet and atorvastatin therapy",
volume = "17",
number = "2",
pages = "217-223",
url = "https://hdl.handle.net/21.15107/rcub_farfar_3054"
}

Ninić, A., Spasojević-Kalimanovska, V., Sopić, M., Munjas, J., Bogavac-Stanojević, N., Jelić-Ivanović, Z., Kotur-Stevuljević, J., Spasić, S., Crevar-Sakač, M., Milenković, M.,& Vujić, Z.. (2018). Paraoxonases gene expression and distribution in rats organs treated with atherogenic diet and atorvastatin therapy. in Indian Journal of Biotechnology
Natl Inst Science Communication-Niscair, New Delhi., 17(2), 217-223.
https://hdl.handle.net/21.15107/rcub_farfar_3054

Ninić A, Spasojević-Kalimanovska V, Sopić M, Munjas J, Bogavac-Stanojević N, Jelić-Ivanović Z, Kotur-Stevuljević J, Spasić S, Crevar-Sakač M, Milenković M, Vujić Z. Paraoxonases gene expression and distribution in rats organs treated with atherogenic diet and atorvastatin therapy. in Indian Journal of Biotechnology. 2018;17(2):217-223.
https://hdl.handle.net/21.15107/rcub_farfar_3054 .

Ninić, Ana, Spasojević-Kalimanovska, Vesna, Sopić, Miron, Munjas, Jelena, Bogavac-Stanojević, Nataša, Jelić-Ivanović, Zorana, Kotur-Stevuljević, Jelena, Spasić, Slavica, Crevar-Sakač, Milkica, Milenković, Marina, Vujić, Zorica, "Paraoxonases gene expression and distribution in rats organs treated with atherogenic diet and atorvastatin therapy" in Indian Journal of Biotechnology, 17, no. 2 (2018):217-223,
https://hdl.handle.net/21.15107/rcub_farfar_3054 .

TY  - JOUR
AU  - Stevanović, Milena
AU  - Đosić, Marija
AU  - Janković, Ana
AU  - Kojić, Vesna
AU  - Vukašinović-Sekulić, Maja
AU  - Stojanović, Jovica
AU  - Odović, Jadranka
AU  - Crevar-Sakač, Milkica
AU  - Rhee, Kyong Yop
AU  - Mišković-Stanković, Vesna
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3123
AB  - Composite coating of antibiotic gentamicin (Gent), natural polymer chitosan (CS), and hydroxyapatite (HAP) was successfully assessed by applying the electrophoretic deposition (EPD) technique. EPD was performed under optimized deposition conditions (5 V, 12 min) on pure titanium plates, to obtain HAP/CS and HAP/CS/Gent composite coatings in a single step from three-component aqueous suspension, with favorable antibacterial properties. Composite coatings were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray photoelectron analysis, confirming the formation of composite HAP/CS and HAP/CS/Gent coatings on the titanium surface, which is due to intermolecular hydrogen bonds. Employing the XRD technique, HAP was detected by obtaining the characteristic diffraction maximums. Good antibacterial activity of the composite coating loaded with antibiotic (HAP/CS/Gent) was confirmed against Staphylococcus aureus and Escherichia coli, pointing to the high potential for bioapplication. Introduction of gentamicin in HAP/CS/Gent coating caused very mild cytotoxicity in the tested cell lines MRC-5 and L929. MTT testing was used to evaluate cell viability, and HAP/CS was classified as noncytotoxic.
PB  - Amer Chemical Soc, Washington
T2  - ACS Biomaterials Science & Engineering
T1  - Gentamicin-Loaded Bioactive Hydroxyapatite/Chitosan Composite Coating Electrodeposited on Titanium
VL  - 4
IS  - 12
SP  - 3994
EP  - 4007
DO  - 10.1021/acsbiomaterials.8b00859
ER  - 

@article{
author = "Stevanović, Milena and Đosić, Marija and Janković, Ana and Kojić, Vesna and Vukašinović-Sekulić, Maja and Stojanović, Jovica and Odović, Jadranka and Crevar-Sakač, Milkica and Rhee, Kyong Yop and Mišković-Stanković, Vesna",
year = "2018",
abstract = "Composite coating of antibiotic gentamicin (Gent), natural polymer chitosan (CS), and hydroxyapatite (HAP) was successfully assessed by applying the electrophoretic deposition (EPD) technique. EPD was performed under optimized deposition conditions (5 V, 12 min) on pure titanium plates, to obtain HAP/CS and HAP/CS/Gent composite coatings in a single step from three-component aqueous suspension, with favorable antibacterial properties. Composite coatings were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray photoelectron analysis, confirming the formation of composite HAP/CS and HAP/CS/Gent coatings on the titanium surface, which is due to intermolecular hydrogen bonds. Employing the XRD technique, HAP was detected by obtaining the characteristic diffraction maximums. Good antibacterial activity of the composite coating loaded with antibiotic (HAP/CS/Gent) was confirmed against Staphylococcus aureus and Escherichia coli, pointing to the high potential for bioapplication. Introduction of gentamicin in HAP/CS/Gent coating caused very mild cytotoxicity in the tested cell lines MRC-5 and L929. MTT testing was used to evaluate cell viability, and HAP/CS was classified as noncytotoxic.",
publisher = "Amer Chemical Soc, Washington",
journal = "ACS Biomaterials Science & Engineering",
title = "Gentamicin-Loaded Bioactive Hydroxyapatite/Chitosan Composite Coating Electrodeposited on Titanium",
volume = "4",
number = "12",
pages = "3994-4007",
doi = "10.1021/acsbiomaterials.8b00859"
}

Stevanović, M., Đosić, M., Janković, A., Kojić, V., Vukašinović-Sekulić, M., Stojanović, J., Odović, J., Crevar-Sakač, M., Rhee, K. Y.,& Mišković-Stanković, V.. (2018). Gentamicin-Loaded Bioactive Hydroxyapatite/Chitosan Composite Coating Electrodeposited on Titanium. in ACS Biomaterials Science & Engineering
Amer Chemical Soc, Washington., 4(12), 3994-4007.
https://doi.org/10.1021/acsbiomaterials.8b00859

Stevanović M, Đosić M, Janković A, Kojić V, Vukašinović-Sekulić M, Stojanović J, Odović J, Crevar-Sakač M, Rhee KY, Mišković-Stanković V. Gentamicin-Loaded Bioactive Hydroxyapatite/Chitosan Composite Coating Electrodeposited on Titanium. in ACS Biomaterials Science & Engineering. 2018;4(12):3994-4007.
doi:10.1021/acsbiomaterials.8b00859 .

Stevanović, Milena, Đosić, Marija, Janković, Ana, Kojić, Vesna, Vukašinović-Sekulić, Maja, Stojanović, Jovica, Odović, Jadranka, Crevar-Sakač, Milkica, Rhee, Kyong Yop, Mišković-Stanković, Vesna, "Gentamicin-Loaded Bioactive Hydroxyapatite/Chitosan Composite Coating Electrodeposited on Titanium" in ACS Biomaterials Science & Engineering, 4, no. 12 (2018):3994-4007,
https://doi.org/10.1021/acsbiomaterials.8b00859 . .

TY  - JOUR
AU  - Crevar-Sakač, Milkica
AU  - Vujić, Zorica
AU  - Kotur-Stevuljević, Jelena
AU  - Ivanišević, Jasmina
AU  - Jelić-Ivanović, Zorana
AU  - Milenković, Marina
AU  - Markelić, Milica
AU  - Vujčić, Zoran
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2689
AB  - Backgroung/Aim. Since combining conventional drugs with herbal medicinal products is in current research focus and possible of great interest as therapy improvement way, the aim of this study was to determine the effects of well-established antiatherosclerotic drug atorvastatin (CAS number 134523-00-5) and commercially available artichoke leaf tincture (ALTINC), used as combined therapy, as well as to compare effects of these two treatments separately. Methods. Experimental animals were divided into five groups: the group I (the control group of rats fed with standard diet during 11 weeks), and the remaining 4 groups of rats (II, III, IV and V) fed with standard diet during the first week and then with hypercholesterolemic diet during the next 10 weeks. The group II of rats were left without treatment, while in the groups III, IV and V were rats treated per os with atorvastatin (1.15 mg/kg body wright - b.w.), ALTINC (0.1 mL/kg b.w.) and their combination in same doses, respectively, for the last six weeks. Results. The cholesterol rich diet led to pronounced hyperlipidemia which could not be overcame with the therapy. However, the therapy showed positive effects on abdominal aorta wall thickness and parameters of oxidative stress (malondialdehyde - MDA, proxidative-antioxidative balance - PAB) and anti- oxidative protection (reduced glutathione - GSH, paraoxanase 1 - PON1, superoxide dismutase - SODA SH groups), especially ALTINC was successful in oxidative status improvement. Conclusion. Separate treatments comparison showed that artichoke leaf tincture is very potent antioxidant with beneficial effects in early stages of atherosclerosis. Since atorvastatin and constituents of ALTINC probably have different mechanisms of action, simultaneous use of both therapies could be beneficial but should be further investigated since our results showed that ALTINC is less effective when used in combination with atorvastatin.
AB  - Uvod/Cilj. Savremena istraživanja sve više se okreću mogućnosti kombinovanja konvencionalne terapije sa biljnim lekovitim proizvodima. Cilj ovog istraživanja bio je praćenje efekata atorvastatina (CAS broj 134523-00-5), poznatog leka koji se koristi u terapiji hiperlipidemije, i tinkture lista artičoke primenjenih pojedinačno, kao i u obliku kombinovane terapije. Metode. Eksperimentalne životinje bile su podeljene u pet grupa: grupa I bila je kontrolna i činili su je pacovi hranjeni standardnom hranom za glodare tokom 11 nedelja, dok su preostale četiri grupe (II-V) činili pacovi koji su hranjeni standardnom hranom tokom prve nedelje, a potom u narednih 10 hranom bogatom holesterolom. Grupa II nije dobijala nikakav tretman, dok su III, IV i V posle 4. nedelje od početka uzimanja hrane bogate holesterolom, tokom narednih šest nedelja tretirane per os, redom: atorvastatinom u dozi od 1,15 mg/kg, tinkturom artičoke u dozi od 0,1 mL/kg i njihovom kombinacijom u istim dozama. Rezultati. Hrana bogata holesterolom izazvala je uznapredovalu hiperholesterolemiju na koju terapija nije značajno delovala. Terapija je pokazala povoljan efekat na debljinu zida trbušne aorte, parametre oksidativnog stresa (malondialdehid - MDA, prooksidativni-antioksidativni balans - PAB) i anti-oksidativne zaštite (redukovani glutation - GSH, SH grupe, paraoksonazu1 - PON1, superoksid dismutazu - SOD). Tinktura lista artičoke pokazala se najboljom u poboljšanju oksidativnog statusa. Zaključak. Poređenje pojedinačne terapije pokazalo je da tinktura lista artičoke ima jako anti-oksidativno dejstvo i pokazuje povoljne efekte u početnim fazama aterosklerotskog procesa. S obzirom na to da atorvastatin i komponente tinkture lista artičoke verovatno deluju različitim mehanizmima, kombinovana primena može imati povoljne efekte, ali se mora dodatno ispitati jer dobijeni rezultati ukazuju da je tinktura lista artičoke manje efikasan kada se primenjuje zajedno sa atorvastatinom.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats
T1  - Uticaj atorvastatina i tinkture lista artičoke na oksidativni stres kod pacova sa hiperholesterolemijom
VL  - 73
IS  - 2
SP  - 178
EP  - 187
DO  - 10.2298/VSP140917148C
ER  - 

@article{
author = "Crevar-Sakač, Milkica and Vujić, Zorica and Kotur-Stevuljević, Jelena and Ivanišević, Jasmina and Jelić-Ivanović, Zorana and Milenković, Marina and Markelić, Milica and Vujčić, Zoran",
year = "2016",
abstract = "Backgroung/Aim. Since combining conventional drugs with herbal medicinal products is in current research focus and possible of great interest as therapy improvement way, the aim of this study was to determine the effects of well-established antiatherosclerotic drug atorvastatin (CAS number 134523-00-5) and commercially available artichoke leaf tincture (ALTINC), used as combined therapy, as well as to compare effects of these two treatments separately. Methods. Experimental animals were divided into five groups: the group I (the control group of rats fed with standard diet during 11 weeks), and the remaining 4 groups of rats (II, III, IV and V) fed with standard diet during the first week and then with hypercholesterolemic diet during the next 10 weeks. The group II of rats were left without treatment, while in the groups III, IV and V were rats treated per os with atorvastatin (1.15 mg/kg body wright - b.w.), ALTINC (0.1 mL/kg b.w.) and their combination in same doses, respectively, for the last six weeks. Results. The cholesterol rich diet led to pronounced hyperlipidemia which could not be overcame with the therapy. However, the therapy showed positive effects on abdominal aorta wall thickness and parameters of oxidative stress (malondialdehyde - MDA, proxidative-antioxidative balance - PAB) and anti- oxidative protection (reduced glutathione - GSH, paraoxanase 1 - PON1, superoxide dismutase - SODA SH groups), especially ALTINC was successful in oxidative status improvement. Conclusion. Separate treatments comparison showed that artichoke leaf tincture is very potent antioxidant with beneficial effects in early stages of atherosclerosis. Since atorvastatin and constituents of ALTINC probably have different mechanisms of action, simultaneous use of both therapies could be beneficial but should be further investigated since our results showed that ALTINC is less effective when used in combination with atorvastatin., Uvod/Cilj. Savremena istraživanja sve više se okreću mogućnosti kombinovanja konvencionalne terapije sa biljnim lekovitim proizvodima. Cilj ovog istraživanja bio je praćenje efekata atorvastatina (CAS broj 134523-00-5), poznatog leka koji se koristi u terapiji hiperlipidemije, i tinkture lista artičoke primenjenih pojedinačno, kao i u obliku kombinovane terapije. Metode. Eksperimentalne životinje bile su podeljene u pet grupa: grupa I bila je kontrolna i činili su je pacovi hranjeni standardnom hranom za glodare tokom 11 nedelja, dok su preostale četiri grupe (II-V) činili pacovi koji su hranjeni standardnom hranom tokom prve nedelje, a potom u narednih 10 hranom bogatom holesterolom. Grupa II nije dobijala nikakav tretman, dok su III, IV i V posle 4. nedelje od početka uzimanja hrane bogate holesterolom, tokom narednih šest nedelja tretirane per os, redom: atorvastatinom u dozi od 1,15 mg/kg, tinkturom artičoke u dozi od 0,1 mL/kg i njihovom kombinacijom u istim dozama. Rezultati. Hrana bogata holesterolom izazvala je uznapredovalu hiperholesterolemiju na koju terapija nije značajno delovala. Terapija je pokazala povoljan efekat na debljinu zida trbušne aorte, parametre oksidativnog stresa (malondialdehid - MDA, prooksidativni-antioksidativni balans - PAB) i anti-oksidativne zaštite (redukovani glutation - GSH, SH grupe, paraoksonazu1 - PON1, superoksid dismutazu - SOD). Tinktura lista artičoke pokazala se najboljom u poboljšanju oksidativnog statusa. Zaključak. Poređenje pojedinačne terapije pokazalo je da tinktura lista artičoke ima jako anti-oksidativno dejstvo i pokazuje povoljne efekte u početnim fazama aterosklerotskog procesa. S obzirom na to da atorvastatin i komponente tinkture lista artičoke verovatno deluju različitim mehanizmima, kombinovana primena može imati povoljne efekte, ali se mora dodatno ispitati jer dobijeni rezultati ukazuju da je tinktura lista artičoke manje efikasan kada se primenjuje zajedno sa atorvastatinom.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats, Uticaj atorvastatina i tinkture lista artičoke na oksidativni stres kod pacova sa hiperholesterolemijom",
volume = "73",
number = "2",
pages = "178-187",
doi = "10.2298/VSP140917148C"
}

Crevar-Sakač, M., Vujić, Z., Kotur-Stevuljević, J., Ivanišević, J., Jelić-Ivanović, Z., Milenković, M., Markelić, M.,& Vujčić, Z.. (2016). Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 73(2), 178-187.
https://doi.org/10.2298/VSP140917148C

Crevar-Sakač M, Vujić Z, Kotur-Stevuljević J, Ivanišević J, Jelić-Ivanović Z, Milenković M, Markelić M, Vujčić Z. Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats. in Vojnosanitetski pregled. 2016;73(2):178-187.
doi:10.2298/VSP140917148C .

Crevar-Sakač, Milkica, Vujić, Zorica, Kotur-Stevuljević, Jelena, Ivanišević, Jasmina, Jelić-Ivanović, Zorana, Milenković, Marina, Markelić, Milica, Vujčić, Zoran, "Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats" in Vojnosanitetski pregled, 73, no. 2 (2016):178-187,
https://doi.org/10.2298/VSP140917148C . .

TY  - JOUR
AU  - Crevar-Sakač, Milkica
AU  - Vujić, Zorica
AU  - Vujčić, Zoran
AU  - Marković, Bojan
AU  - Vasiljević, Dragana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2623
AB  - A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the quantification of atorvastatin, ortho-hydroxyatorvastatin, para-hydroxyatorvastatin, and atorvastatin lactone in rat plasma. Solid-phase extraction was used for preparation of samples. Rosuvastatin was chosen as an internal standard. Chromatographic separation was achieved on ZORBAX Eclipse C-18 Analytical, 4.6 x 100 mm (3.5 mu m) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 mu L min(-1). The column was kept at constant temperature (25 degrees C), and autosampler tray temperature was set at 4 degrees C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 -> Q3, collision energy) atorvastatin (559.47 -> 440.03, 22 eV), atorvastatin lactone (541.36 -> 448.02, 19 eV), orthohydroxyatorvastatin (575.20 -> 440.18, 20 eV), para-hydroxyatorvastatin (575.54 -> 440.18, 20 eV), and rosuvastatin (482.25 with selected combination of two fragments 257.77, 31 eV, and 299.81, 35 eV) in positive ion mode. The method was validated over a concentration range of 0.5-20 ng mL(-1) for ortho-hydroxyatorvastatin and para-hydroxyatorvastatin and 0.1-20 ng mL(-1) for atorvastatin and atorvastatin lactone with excellent linearity (r(2) >= 0.99). This method demonstrated acceptable precision and accuracy at four quality control concentration levels. The detection limits were 0.1 and 0.13 ng mL(-1) for orthohydroxyatorvastatin and para-hydroxyatorvastatin, respectively, and 0.05 ng mL(-1) for atorvastatin and atorvastatin lactone. All analytes were found to be stable at examined conditions. Validated method was applied for determination of atorvastatin and its metabolites in plasma of experimental animals.
PB  - Akademiai Kiado Rt, Budapest
T2  - Acta Chromatographica
T1  - LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma
VL  - 28
IS  - 3
SP  - 281
EP  - 298
DO  - 10.1556/1326.2016.28.3.1
ER  - 

@article{
author = "Crevar-Sakač, Milkica and Vujić, Zorica and Vujčić, Zoran and Marković, Bojan and Vasiljević, Dragana",
year = "2016",
abstract = "A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the quantification of atorvastatin, ortho-hydroxyatorvastatin, para-hydroxyatorvastatin, and atorvastatin lactone in rat plasma. Solid-phase extraction was used for preparation of samples. Rosuvastatin was chosen as an internal standard. Chromatographic separation was achieved on ZORBAX Eclipse C-18 Analytical, 4.6 x 100 mm (3.5 mu m) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 mu L min(-1). The column was kept at constant temperature (25 degrees C), and autosampler tray temperature was set at 4 degrees C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 -> Q3, collision energy) atorvastatin (559.47 -> 440.03, 22 eV), atorvastatin lactone (541.36 -> 448.02, 19 eV), orthohydroxyatorvastatin (575.20 -> 440.18, 20 eV), para-hydroxyatorvastatin (575.54 -> 440.18, 20 eV), and rosuvastatin (482.25 with selected combination of two fragments 257.77, 31 eV, and 299.81, 35 eV) in positive ion mode. The method was validated over a concentration range of 0.5-20 ng mL(-1) for ortho-hydroxyatorvastatin and para-hydroxyatorvastatin and 0.1-20 ng mL(-1) for atorvastatin and atorvastatin lactone with excellent linearity (r(2) >= 0.99). This method demonstrated acceptable precision and accuracy at four quality control concentration levels. The detection limits were 0.1 and 0.13 ng mL(-1) for orthohydroxyatorvastatin and para-hydroxyatorvastatin, respectively, and 0.05 ng mL(-1) for atorvastatin and atorvastatin lactone. All analytes were found to be stable at examined conditions. Validated method was applied for determination of atorvastatin and its metabolites in plasma of experimental animals.",
publisher = "Akademiai Kiado Rt, Budapest",
journal = "Acta Chromatographica",
title = "LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma",
volume = "28",
number = "3",
pages = "281-298",
doi = "10.1556/1326.2016.28.3.1"
}

Crevar-Sakač, M., Vujić, Z., Vujčić, Z., Marković, B.,& Vasiljević, D.. (2016). LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma. in Acta Chromatographica
Akademiai Kiado Rt, Budapest., 28(3), 281-298.
https://doi.org/10.1556/1326.2016.28.3.1

Crevar-Sakač M, Vujić Z, Vujčić Z, Marković B, Vasiljević D. LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma. in Acta Chromatographica. 2016;28(3):281-298.
doi:10.1556/1326.2016.28.3.1 .

Crevar-Sakač, Milkica, Vujić, Zorica, Vujčić, Zoran, Marković, Bojan, Vasiljević, Dragana, "LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma" in Acta Chromatographica, 28, no. 3 (2016):281-298,
https://doi.org/10.1556/1326.2016.28.3.1 . .

TY  - JOUR
AU  - Milašinović, Nikola
AU  - Čalija, Bojan
AU  - Vidović, Bojana
AU  - Crevar-Sakač, Milkica
AU  - Vujić, Zorica
AU  - Knežević-Jugović, Zorica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2607
AB  - The aim of this study was to investigate the encapsulation of a-lipoic acid (LA) onto chitosan microbeads in order to achieve a sustained release. Microbeads of different compositions were synthetized by inverse emulsion method, and characterized by in vitro swelling and drug release studies, FT-IR, DSC and SEM analyses. The encapsulation of LA was performed by swelling of previously synthetized dry microbeads in LA solution. The encapsulation efficiency was determined in terms of LA concentration, using liquid chromatography tandem mass spectrometry (LC-MS/MS). The swelling of synthetized microbeads was well pronounced in the acidic media. FT-IR analysis confirmed the presence of LA in microbeads and its interactions with matrices, which was in agreement with the results revealed by DSC analysis. SEM analysis revealed the porous structure, micron-size and spherical shape of the synthetized beads. Encapsulation efficiency was in the range from 46.8 to 58.5% depending on the hydrogel composition. The microbeads exhibited sustained release of LA under conditions mimicking gastrointestinal tract. Results of antioxidant activity of released LA showed good correlation with the concentration of the released LA. The obtained results suggested that synthetized microbeads have promising potential for oral administration with reduced dosing frequency in comparison to the immediate release formulations.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of the Taiwan Institute of Chemical Engineers
T1  - Sustained release of alpha-lipoic acid from chitosan microbeads synthetized by inverse emulsion method
VL  - 60
SP  - 106
EP  - 112
DO  - 10.1016/j.jtice.2015.10.037
ER  - 

@article{
author = "Milašinović, Nikola and Čalija, Bojan and Vidović, Bojana and Crevar-Sakač, Milkica and Vujić, Zorica and Knežević-Jugović, Zorica",
year = "2016",
abstract = "The aim of this study was to investigate the encapsulation of a-lipoic acid (LA) onto chitosan microbeads in order to achieve a sustained release. Microbeads of different compositions were synthetized by inverse emulsion method, and characterized by in vitro swelling and drug release studies, FT-IR, DSC and SEM analyses. The encapsulation of LA was performed by swelling of previously synthetized dry microbeads in LA solution. The encapsulation efficiency was determined in terms of LA concentration, using liquid chromatography tandem mass spectrometry (LC-MS/MS). The swelling of synthetized microbeads was well pronounced in the acidic media. FT-IR analysis confirmed the presence of LA in microbeads and its interactions with matrices, which was in agreement with the results revealed by DSC analysis. SEM analysis revealed the porous structure, micron-size and spherical shape of the synthetized beads. Encapsulation efficiency was in the range from 46.8 to 58.5% depending on the hydrogel composition. The microbeads exhibited sustained release of LA under conditions mimicking gastrointestinal tract. Results of antioxidant activity of released LA showed good correlation with the concentration of the released LA. The obtained results suggested that synthetized microbeads have promising potential for oral administration with reduced dosing frequency in comparison to the immediate release formulations.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of the Taiwan Institute of Chemical Engineers",
title = "Sustained release of alpha-lipoic acid from chitosan microbeads synthetized by inverse emulsion method",
volume = "60",
pages = "106-112",
doi = "10.1016/j.jtice.2015.10.037"
}

Milašinović, N., Čalija, B., Vidović, B., Crevar-Sakač, M., Vujić, Z.,& Knežević-Jugović, Z.. (2016). Sustained release of alpha-lipoic acid from chitosan microbeads synthetized by inverse emulsion method. in Journal of the Taiwan Institute of Chemical Engineers
Elsevier Science BV, Amsterdam., 60, 106-112.
https://doi.org/10.1016/j.jtice.2015.10.037

Milašinović N, Čalija B, Vidović B, Crevar-Sakač M, Vujić Z, Knežević-Jugović Z. Sustained release of alpha-lipoic acid from chitosan microbeads synthetized by inverse emulsion method. in Journal of the Taiwan Institute of Chemical Engineers. 2016;60:106-112.
doi:10.1016/j.jtice.2015.10.037 .

Milašinović, Nikola, Čalija, Bojan, Vidović, Bojana, Crevar-Sakač, Milkica, Vujić, Zorica, Knežević-Jugović, Zorica, "Sustained release of alpha-lipoic acid from chitosan microbeads synthetized by inverse emulsion method" in Journal of the Taiwan Institute of Chemical Engineers, 60 (2016):106-112,
https://doi.org/10.1016/j.jtice.2015.10.037 . .

TY  - THES
AU  - Crevar-Sakač, Milkica
PY  - 2015
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=2460
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:10475/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=47557391
UR  - http://nardus.mpn.gov.rs/123456789/4651
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3384
AB  - Atorvastatin pripada grupi antihiperlipidemijskih lekova poznatih pod nazivom statini.Osnovni mehanizam delovanja ovih lekova je specifična, kompetitivna i reverzibilnainhibicija HMG-CoA reduktaze, enzima koji je značajan za proces biosinteze holesterola.Osim direktnog dejstva na biosintezu holesterola, atorvastatin pokazuje niz plejotropnihefekata koji imaju povoljno dejstvo na aterosklerotske promene. Atorvastatin metaboliše ujetri pod dejstvom CYP3A4 enzima pri čemu nastaju dva aktivna metabolita: ortohidroksiatorvastatini para-hidroksiatorvastatin i tri neaktivna metabolita: atorvastatin-lakton,orto-hidroksiatorvastatin-lakton i para-hidroksiatorvastatin-lakton.Artičoka (Cynara scolymus L., Asteraceae) je zeljasta, jednogodišnja biljkarasprostranjena širom Mediterana. Terapija hiperlipidemija, pored lekova uključuje inefarmakološke mere (promena ishrane, fizičke vežbe, prestanak pušenja i unošenja alkohola,primena biljnih ekstrakata). Obzirom da su svi delovi artičoke bogati jedinjenjima koja seponašaju kao prirodni antioksidansi, ekstrakt lista artičoke i atorvastatin se često u terapijiprimenjuju zajedno.Cilj doktorske disertacije je da se ispita uticaj vodeno-etanolnog ekstrakta lista artičoke(Tinctura Cynarae) na metabolizam atorvastatina i opravdanost istovremene primeneatorvastatina i navedenog biljnog ekstrakta. Za ispitivanja su korišćene komercijalne biljnekapi na bazi artičoke u kojima je kvantifikovan sadržaj cinarina i hlorogenske kiselineprimenom HPLC metode (određen sadržaj obe komponente je 0,2 %).Eksperimentalni rad je zasnovan na određivanju i praćenju promene koncentracijemetabolita atorvastatina: orto-hidroksiatorvastatina, para-hidroksiatorvastatina i atorvastatinlaktonau uzorcima plazme eksperimentalnih životinja koje su bile na aterogenoj ishrani i kojesu primale atorvastatin kao monoterapiju ili zajedno sa ekstraktom lista artičoke. Za izvođenjeeksperimenta korišćeni su pacovi soja Wistar. Životinje su podeljene u 5 grupa koje su bile narazličitoj ishrani i/ili terapiji. Jedna grupa životinja je tokom celog eksperimenta bila nanormalnoj ishrani, dok su preostale četiri grupe do kraja eksperimenta bile na aterogenojishrani. U skladu sa prethodno postavljenim planom eksperimenta, različite grupe životinja naaterogenoj ishrani su, posle određenog vremena, primale atorvastatin, ili atorvastatin i ekstraktlista artičoke, ili samo ekstrakt lista artičoke...
AB  - Atorvastatin belongs to the group of antihyperlipidemic drugs known as statins. Thebasic mechanism of action of these drugs is specific, competitive and reversible inhibition ofHMG-CoA reductase, an enzyme involved in cholesterol biosynthesis. In addition,atorvastatin shows many beneficial pleiotropic effects. Atorvastatin is metabolized in the liverunder the influence of the CYP3A4 enzyme to two active metabolites: orthohydroxyatorvastatinand para-hydroxyatorvastatin and three inactive metabolites: orthohydroxyatorvastatinlactone, para-hydroxyatorvastatin lactone and atorvastatin lactone.Artichoke (Cynara scolymus L., Asteraceae) is annual plant, distributed throughoutMediterranean. The treatment of hyperlipidemia, in addition to pharmacotherapy, includesnonpharmacological measures (diet changes, physical activity, cessation of smoking andalcohol intake, use of herbal extracts). Since all the parts of artichoke plant are rich in naturalantioxidants, artichoke leaf extract and atorvastatin are often used together.The Ph. D. disertation is focused to investigate the effect of aqueous-ethanolic extractof artichoke (Tinctura Cynarae) on the metabolism of atorvastatin and justification of coadministrationof atorvastatin and herbal extract mentioned above. Experiments wereconducted using commercial artichoke preparation. The contents of chlorogenic acid andcynarin in Tinctura Cynarae were quantified by means of the HPLC method (determinedcontent of both components is 0.2 %).Experimental work is based on determination and monitoring changes in theconcentration of atorvastatin metabolites: ortho-hydroxyatorvastatin, parahydroxyatorvastatinand atorvastatin lactone in the plasma samples of experimental animalsfed with atherogenic diet and treated with atorvastatin (alone or in combination with artichokeleaf extract). Experiments were conducted on experimental animals (Wistar rats). The animalswere divided into 5 groups on different diet and/or therapy. One group of animals was onnormal diet all the time during experiment, and the remaining four groups were on theatherogenic diet. Three of these four groups were treated with: atorvastatin, artichoke leafextract and the combination of atorvastatin and artichoke leaf extract...
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Uticaj ekstrakta lista artičoke na metabolizam atorvastatina i optimizacija metoda tečne hromatografije za praćenje nastalih metabolita u biološkom materijalu
T1  - Influence of artichoke leaf extract on atorvastatin metabolism and optimization of liquid chromatography methods for determination of atorvastatin and metabolites in biological material
UR  - https://hdl.handle.net/21.15107/rcub_nardus_4651
ER  - 

@phdthesis{
author = "Crevar-Sakač, Milkica",
year = "2015",
abstract = "Atorvastatin pripada grupi antihiperlipidemijskih lekova poznatih pod nazivom statini.Osnovni mehanizam delovanja ovih lekova je specifična, kompetitivna i reverzibilnainhibicija HMG-CoA reduktaze, enzima koji je značajan za proces biosinteze holesterola.Osim direktnog dejstva na biosintezu holesterola, atorvastatin pokazuje niz plejotropnihefekata koji imaju povoljno dejstvo na aterosklerotske promene. Atorvastatin metaboliše ujetri pod dejstvom CYP3A4 enzima pri čemu nastaju dva aktivna metabolita: ortohidroksiatorvastatini para-hidroksiatorvastatin i tri neaktivna metabolita: atorvastatin-lakton,orto-hidroksiatorvastatin-lakton i para-hidroksiatorvastatin-lakton.Artičoka (Cynara scolymus L., Asteraceae) je zeljasta, jednogodišnja biljkarasprostranjena širom Mediterana. Terapija hiperlipidemija, pored lekova uključuje inefarmakološke mere (promena ishrane, fizičke vežbe, prestanak pušenja i unošenja alkohola,primena biljnih ekstrakata). Obzirom da su svi delovi artičoke bogati jedinjenjima koja seponašaju kao prirodni antioksidansi, ekstrakt lista artičoke i atorvastatin se često u terapijiprimenjuju zajedno.Cilj doktorske disertacije je da se ispita uticaj vodeno-etanolnog ekstrakta lista artičoke(Tinctura Cynarae) na metabolizam atorvastatina i opravdanost istovremene primeneatorvastatina i navedenog biljnog ekstrakta. Za ispitivanja su korišćene komercijalne biljnekapi na bazi artičoke u kojima je kvantifikovan sadržaj cinarina i hlorogenske kiselineprimenom HPLC metode (određen sadržaj obe komponente je 0,2 %).Eksperimentalni rad je zasnovan na određivanju i praćenju promene koncentracijemetabolita atorvastatina: orto-hidroksiatorvastatina, para-hidroksiatorvastatina i atorvastatinlaktonau uzorcima plazme eksperimentalnih životinja koje su bile na aterogenoj ishrani i kojesu primale atorvastatin kao monoterapiju ili zajedno sa ekstraktom lista artičoke. Za izvođenjeeksperimenta korišćeni su pacovi soja Wistar. Životinje su podeljene u 5 grupa koje su bile narazličitoj ishrani i/ili terapiji. Jedna grupa životinja je tokom celog eksperimenta bila nanormalnoj ishrani, dok su preostale četiri grupe do kraja eksperimenta bile na aterogenojishrani. U skladu sa prethodno postavljenim planom eksperimenta, različite grupe životinja naaterogenoj ishrani su, posle određenog vremena, primale atorvastatin, ili atorvastatin i ekstraktlista artičoke, ili samo ekstrakt lista artičoke..., Atorvastatin belongs to the group of antihyperlipidemic drugs known as statins. Thebasic mechanism of action of these drugs is specific, competitive and reversible inhibition ofHMG-CoA reductase, an enzyme involved in cholesterol biosynthesis. In addition,atorvastatin shows many beneficial pleiotropic effects. Atorvastatin is metabolized in the liverunder the influence of the CYP3A4 enzyme to two active metabolites: orthohydroxyatorvastatinand para-hydroxyatorvastatin and three inactive metabolites: orthohydroxyatorvastatinlactone, para-hydroxyatorvastatin lactone and atorvastatin lactone.Artichoke (Cynara scolymus L., Asteraceae) is annual plant, distributed throughoutMediterranean. The treatment of hyperlipidemia, in addition to pharmacotherapy, includesnonpharmacological measures (diet changes, physical activity, cessation of smoking andalcohol intake, use of herbal extracts). Since all the parts of artichoke plant are rich in naturalantioxidants, artichoke leaf extract and atorvastatin are often used together.The Ph. D. disertation is focused to investigate the effect of aqueous-ethanolic extractof artichoke (Tinctura Cynarae) on the metabolism of atorvastatin and justification of coadministrationof atorvastatin and herbal extract mentioned above. Experiments wereconducted using commercial artichoke preparation. The contents of chlorogenic acid andcynarin in Tinctura Cynarae were quantified by means of the HPLC method (determinedcontent of both components is 0.2 %).Experimental work is based on determination and monitoring changes in theconcentration of atorvastatin metabolites: ortho-hydroxyatorvastatin, parahydroxyatorvastatinand atorvastatin lactone in the plasma samples of experimental animalsfed with atherogenic diet and treated with atorvastatin (alone or in combination with artichokeleaf extract). Experiments were conducted on experimental animals (Wistar rats). The animalswere divided into 5 groups on different diet and/or therapy. One group of animals was onnormal diet all the time during experiment, and the remaining four groups were on theatherogenic diet. Three of these four groups were treated with: atorvastatin, artichoke leafextract and the combination of atorvastatin and artichoke leaf extract...",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Uticaj ekstrakta lista artičoke na metabolizam atorvastatina i optimizacija metoda tečne hromatografije za praćenje nastalih metabolita u biološkom materijalu, Influence of artichoke leaf extract on atorvastatin metabolism and optimization of liquid chromatography methods for determination of atorvastatin and metabolites in biological material",
url = "https://hdl.handle.net/21.15107/rcub_nardus_4651"
}

Crevar-Sakač, M.. (2015). Uticaj ekstrakta lista artičoke na metabolizam atorvastatina i optimizacija metoda tečne hromatografije za praćenje nastalih metabolita u biološkom materijalu. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_4651

Crevar-Sakač M. Uticaj ekstrakta lista artičoke na metabolizam atorvastatina i optimizacija metoda tečne hromatografije za praćenje nastalih metabolita u biološkom materijalu. in Универзитет у Београду. 2015;.
https://hdl.handle.net/21.15107/rcub_nardus_4651 .

Crevar-Sakač, Milkica, "Uticaj ekstrakta lista artičoke na metabolizam atorvastatina i optimizacija metoda tečne hromatografije za praćenje nastalih metabolita u biološkom materijalu" in Универзитет у Београду (2015),
https://hdl.handle.net/21.15107/rcub_nardus_4651 .

TY  - CONF
AU  - Vidović, Bojana
AU  - Milašinović, Nikola
AU  - Vidović, Jana
AU  - Čalija, Bojan
AU  - Crevar-Sakač, Milkica
AU  - Vujić, Zorica
AU  - Milić, Jela
AU  - Đorđević, Brižita
AU  - Kalagasidis-Krusić, Melina T.
AU  - Knežević-Jugović, Zorica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2333
AB  - Introduction: Αlpha-Lipoic acid (LA) has gained considerable
attention as a nutraceutical agent due to its various medicinal proper-
ties. Despite its safety and effectiveness LA utilization is limited by its
low bioavailability and stability. Recently, there has been an increasing
interest in the developing of efficient oral delivery systems, such as
LA/chitosan conjugate, for protection and controlled release of LA to
enhance its oral bioavailability with improved biological potential.
Objectives: The aim of the research was to explore, both in vitro
antioxidative activity of LA upon encapsulation into chitosan micro-
particles (LA/chitosan conjugate formation) and its release.
Method / Design: LA was encapsulated by dip-coating method
onto ready-made chitosan microparticles of predetermined particle
size, prepared by reverse emulsion polymerization technique and
the encapsulation efficiency was determined, as well. Structural
interactions of LA with chitosan within the conjugate were revealed
by Fourier Transform Infrared (FT-IR) spectroscopy and Differental
Scanning Calorimetry (DSC). Also, the prepared LA/chitosan conjugates were evaluated for in vitro released LA antioxidative activity.
Results: The applied technique allowed the production of chitosan microparticles with an average diameter between 135 μm and 169
μm, in its dried state. Furthermore, the encapsulation efficiency of LA 12th European Nutrition Conference 2015Ann Nutr Metab 2015; 67(suppl 1) 485
was up to 50%. FT-IR analyses confirmed the presence of LA within
synthetized microparticles. The disappearance of melting peak of pure
LA upon encapsulation, observed at DSC thermogram, could be ascribed to the formation of LA/chitosan conjugate. A satisfactory level of
antioxidative activity after sustained release of LA in pH 6.8 has been
confirmed by FRAP (showing up to 56 μmolFe(II)/gmicroparticles)
and ABTS (showing up to 85 μmolTrolox/gmicroparticles) assays.
Conclusions: The results showed that the prepared LA/chitosan
microparticles conjugate could be used for encapsulation of LA and
exhibited the potential of preserving its activity for a longer period of
time, by improving its stability and functionality.
PB  - Karger, Basel
C3  - Annals of Nutrition and Metabolism
T1  - Preparation of α-lipoic acid/chitosan microparticle conjugate and its in vitro
antioxidative activity
VL  - 67
IS  - Supplement 1
SP  - 484
EP  - 485
DO  - 10.1159/000440895
ER  - 

@conference{
author = "Vidović, Bojana and Milašinović, Nikola and Vidović, Jana and Čalija, Bojan and Crevar-Sakač, Milkica and Vujić, Zorica and Milić, Jela and Đorđević, Brižita and Kalagasidis-Krusić, Melina T. and Knežević-Jugović, Zorica",
year = "2015",
abstract = "Introduction: Αlpha-Lipoic acid (LA) has gained considerable
attention as a nutraceutical agent due to its various medicinal proper-
ties. Despite its safety and effectiveness LA utilization is limited by its
low bioavailability and stability. Recently, there has been an increasing
interest in the developing of efficient oral delivery systems, such as
LA/chitosan conjugate, for protection and controlled release of LA to
enhance its oral bioavailability with improved biological potential.
Objectives: The aim of the research was to explore, both in vitro
antioxidative activity of LA upon encapsulation into chitosan micro-
particles (LA/chitosan conjugate formation) and its release.
Method / Design: LA was encapsulated by dip-coating method
onto ready-made chitosan microparticles of predetermined particle
size, prepared by reverse emulsion polymerization technique and
the encapsulation efficiency was determined, as well. Structural
interactions of LA with chitosan within the conjugate were revealed
by Fourier Transform Infrared (FT-IR) spectroscopy and Differental
Scanning Calorimetry (DSC). Also, the prepared LA/chitosan conjugates were evaluated for in vitro released LA antioxidative activity.
Results: The applied technique allowed the production of chitosan microparticles with an average diameter between 135 μm and 169
μm, in its dried state. Furthermore, the encapsulation efficiency of LA 12th European Nutrition Conference 2015Ann Nutr Metab 2015; 67(suppl 1) 485
was up to 50%. FT-IR analyses confirmed the presence of LA within
synthetized microparticles. The disappearance of melting peak of pure
LA upon encapsulation, observed at DSC thermogram, could be ascribed to the formation of LA/chitosan conjugate. A satisfactory level of
antioxidative activity after sustained release of LA in pH 6.8 has been
confirmed by FRAP (showing up to 56 μmolFe(II)/gmicroparticles)
and ABTS (showing up to 85 μmolTrolox/gmicroparticles) assays.
Conclusions: The results showed that the prepared LA/chitosan
microparticles conjugate could be used for encapsulation of LA and
exhibited the potential of preserving its activity for a longer period of
time, by improving its stability and functionality.",
publisher = "Karger, Basel",
journal = "Annals of Nutrition and Metabolism",
title = "Preparation of α-lipoic acid/chitosan microparticle conjugate and its in vitro
antioxidative activity",
volume = "67",
number = "Supplement 1",
pages = "484-485",
doi = "10.1159/000440895"
}

Vidović, B., Milašinović, N., Vidović, J., Čalija, B., Crevar-Sakač, M., Vujić, Z., Milić, J., Đorđević, B., Kalagasidis-Krusić, M. T.,& Knežević-Jugović, Z.. (2015). Preparation of α-lipoic acid/chitosan microparticle conjugate and its in vitro
antioxidative activity. in Annals of Nutrition and Metabolism
Karger, Basel., 67(Supplement 1), 484-485.
https://doi.org/10.1159/000440895

Vidović B, Milašinović N, Vidović J, Čalija B, Crevar-Sakač M, Vujić Z, Milić J, Đorđević B, Kalagasidis-Krusić MT, Knežević-Jugović Z. Preparation of α-lipoic acid/chitosan microparticle conjugate and its in vitro
antioxidative activity. in Annals of Nutrition and Metabolism. 2015;67(Supplement 1):484-485.
doi:10.1159/000440895 .

Vidović, Bojana, Milašinović, Nikola, Vidović, Jana, Čalija, Bojan, Crevar-Sakač, Milkica, Vujić, Zorica, Milić, Jela, Đorđević, Brižita, Kalagasidis-Krusić, Melina T., Knežević-Jugović, Zorica, "Preparation of α-lipoic acid/chitosan microparticle conjugate and its in vitro
antioxidative activity" in Annals of Nutrition and Metabolism, 67, no. Supplement 1 (2015):484-485,
https://doi.org/10.1159/000440895 . .

TY  - JOUR
AU  - Ivković, Branka
AU  - Crevar-Sakač, Milkica
AU  - Vujić, Zorica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2280
AB  - In this paper, influence of temperature and light on stability of montelukast in solutions (standard substance, chewable tablets and film coated tablets) which were prepared during routine analysis of related substances was investigated. The content of montelukast and degradation products was determined by HPLC method at defined time intervals (influence of temperature was tested at the beginning, after 24 hours, and after 48 hours, and influence of light was tested at the beginning of the experiment and after 12 hours). Stability of montelukast in tested solutions under influence of temperature was acceptable. The content of montelukast ranged from 98 % to100 %, which meets the pharmacopoeia requirements and specifications. Individual and total impurities were within acceptable limits. Presence of photosensitive functional groups in structure of montelukast led to significant photodegradation. Individual and total impurities in samples which were under influence of light were above acceptable limits. Photodegradation occured during first 12 hours. Content of MOK-3 sulphoxide and unknown impurity on RRT 0.76 was above limits in all examined samples. Over a period of 12 h the content of those impurities grew 8-40 fold compared to time zero values.
AB  - U radu je dat prikaz ispitivanja uticaja temperature i svetlosti na stabilnost montelukasta u rastvorima (standardne supstance, tabletama za žvakanje i filmom obloženih tableta) koji se pripremaju u rutinskoj analizi u toku postupka ispitivanja prisustva srodnih supstanci. Sadržaj montelukasta i nastalih degradacionih proizvoda praćen je primenom RP-HPLC metode u definisanim vremenskim intervalima (0, 24 i 48h kada je u pitanju temperatura, odnosno 0 i 12h kada je u pitanju svetlost). Rezultati ispitivanja uticaja temperature, kao spoljašnjeg faktora nestabilnosti, ukazuju da su analizirani rastvori standarda montelukasta, tableta za žvakanje i filmom obloženih tableta stabilni u prihvatljivim granicama. Sadržaj montelukasta se kreće od 98 % - 100 % što zadovoljava farmakopejske zahteve, kao i zahteve specifikacije proizvoda. Pojedinačne i ukupne nečistoće su u dozvoljenim granicama. Prisustvo fotoreaktivnih funkcionalnih grupa u strukturi montelukasta uslovilo je nastanak fotodegradacionih proizvoda u količinama koje su izvan granica definisanih u monografiji montelukasta, kao i granica definisanih u specifikaciji gotovog proizvoda. Do fotodegradacije dolazi već u toku prvih 12 h. Porast sadržaja MOK-3 sulfoksida i nečistoće sa relativnim retencionim vremenom oko 0,76 zabeležen je u sva tri ispitivana uzorka. U vremenskom intervalu od 12 h uočen je porast sadržaja navedenih nečistoća 8-40 puta u poređenju sa vrednostima u početnom vremenu ispitivanja.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Chemical stability of drugs: Influence of light and temperature on montelukast stability in solution
T1  - Hemijska stabilnost lekova - uticaj svetlosti i temperature na stabilnost montelukasta u rastvoru
VL  - 64
IS  - 2
SP  - 144
EP  - 163
DO  - 10.5937/arhfarm1402144I
ER  - 

@article{
author = "Ivković, Branka and Crevar-Sakač, Milkica and Vujić, Zorica",
year = "2014",
abstract = "In this paper, influence of temperature and light on stability of montelukast in solutions (standard substance, chewable tablets and film coated tablets) which were prepared during routine analysis of related substances was investigated. The content of montelukast and degradation products was determined by HPLC method at defined time intervals (influence of temperature was tested at the beginning, after 24 hours, and after 48 hours, and influence of light was tested at the beginning of the experiment and after 12 hours). Stability of montelukast in tested solutions under influence of temperature was acceptable. The content of montelukast ranged from 98 % to100 %, which meets the pharmacopoeia requirements and specifications. Individual and total impurities were within acceptable limits. Presence of photosensitive functional groups in structure of montelukast led to significant photodegradation. Individual and total impurities in samples which were under influence of light were above acceptable limits. Photodegradation occured during first 12 hours. Content of MOK-3 sulphoxide and unknown impurity on RRT 0.76 was above limits in all examined samples. Over a period of 12 h the content of those impurities grew 8-40 fold compared to time zero values., U radu je dat prikaz ispitivanja uticaja temperature i svetlosti na stabilnost montelukasta u rastvorima (standardne supstance, tabletama za žvakanje i filmom obloženih tableta) koji se pripremaju u rutinskoj analizi u toku postupka ispitivanja prisustva srodnih supstanci. Sadržaj montelukasta i nastalih degradacionih proizvoda praćen je primenom RP-HPLC metode u definisanim vremenskim intervalima (0, 24 i 48h kada je u pitanju temperatura, odnosno 0 i 12h kada je u pitanju svetlost). Rezultati ispitivanja uticaja temperature, kao spoljašnjeg faktora nestabilnosti, ukazuju da su analizirani rastvori standarda montelukasta, tableta za žvakanje i filmom obloženih tableta stabilni u prihvatljivim granicama. Sadržaj montelukasta se kreće od 98 % - 100 % što zadovoljava farmakopejske zahteve, kao i zahteve specifikacije proizvoda. Pojedinačne i ukupne nečistoće su u dozvoljenim granicama. Prisustvo fotoreaktivnih funkcionalnih grupa u strukturi montelukasta uslovilo je nastanak fotodegradacionih proizvoda u količinama koje su izvan granica definisanih u monografiji montelukasta, kao i granica definisanih u specifikaciji gotovog proizvoda. Do fotodegradacije dolazi već u toku prvih 12 h. Porast sadržaja MOK-3 sulfoksida i nečistoće sa relativnim retencionim vremenom oko 0,76 zabeležen je u sva tri ispitivana uzorka. U vremenskom intervalu od 12 h uočen je porast sadržaja navedenih nečistoća 8-40 puta u poređenju sa vrednostima u početnom vremenu ispitivanja.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Chemical stability of drugs: Influence of light and temperature on montelukast stability in solution, Hemijska stabilnost lekova - uticaj svetlosti i temperature na stabilnost montelukasta u rastvoru",
volume = "64",
number = "2",
pages = "144-163",
doi = "10.5937/arhfarm1402144I"
}

Ivković, B., Crevar-Sakač, M.,& Vujić, Z.. (2014). Chemical stability of drugs: Influence of light and temperature on montelukast stability in solution. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 64(2), 144-163.
https://doi.org/10.5937/arhfarm1402144I

Ivković B, Crevar-Sakač M, Vujić Z. Chemical stability of drugs: Influence of light and temperature on montelukast stability in solution. in Arhiv za farmaciju. 2014;64(2):144-163.
doi:10.5937/arhfarm1402144I .

Ivković, Branka, Crevar-Sakač, Milkica, Vujić, Zorica, "Chemical stability of drugs: Influence of light and temperature on montelukast stability in solution" in Arhiv za farmaciju, 64, no. 2 (2014):144-163,
https://doi.org/10.5937/arhfarm1402144I . .

TY  - JOUR
AU  - Crevar-Sakač, Milkica
AU  - Vujić, Zorica
AU  - Brborić, Jasmina
AU  - Kuntić, Vesna
AU  - Uskoković-Marković, Snežana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1928
AB  - The aim of the present study was to optimize a chromatographic method for the analysis of atorvastatin (acid and lactone forms), ortho- and para-hydroxyatorvastatin by using an experimental design approach. Optimization experiments were conducted through a process of screening and optimization. The purpose of a screening design is to identify the factors that have significant effects on the selected chromatographic responses, and for this purpose a full 23 factorial design was used. The location of the true optimum was established by applying Derringer's desirability function, which provides simultaneously optimization of all seven responses. The ranges of the independent variables used for the optimization were content of acetonitrile in mobile phase (60-70%), temperature of column (30-40 C degrees) and flow rate (0.8-1.2 mL min(-1)). The influences of these independent variables were evaluated for the output responses: retention time of first peak (p-hydroxyatorvastatin) and of last peak (atorvastatin, lactone form), symmetries of all four peaks and relative retention time of p-hydroxyatorvastatin. The primary goal of this investigation was establishing a new simple and sensitive method that could be used in analysis of biological samples. The method was validated and successfully applied for determination of atorvastatin (acid and lactone forms) and its metabolites in plasma.
PB  - MDPI, Basel
T2  - Molecules
T1  - An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma
VL  - 18
IS  - 3
SP  - 2469
EP  - 2482
DO  - 10.3390/molecules18032469
ER  - 

@article{
author = "Crevar-Sakač, Milkica and Vujić, Zorica and Brborić, Jasmina and Kuntić, Vesna and Uskoković-Marković, Snežana",
year = "2013",
abstract = "The aim of the present study was to optimize a chromatographic method for the analysis of atorvastatin (acid and lactone forms), ortho- and para-hydroxyatorvastatin by using an experimental design approach. Optimization experiments were conducted through a process of screening and optimization. The purpose of a screening design is to identify the factors that have significant effects on the selected chromatographic responses, and for this purpose a full 23 factorial design was used. The location of the true optimum was established by applying Derringer's desirability function, which provides simultaneously optimization of all seven responses. The ranges of the independent variables used for the optimization were content of acetonitrile in mobile phase (60-70%), temperature of column (30-40 C degrees) and flow rate (0.8-1.2 mL min(-1)). The influences of these independent variables were evaluated for the output responses: retention time of first peak (p-hydroxyatorvastatin) and of last peak (atorvastatin, lactone form), symmetries of all four peaks and relative retention time of p-hydroxyatorvastatin. The primary goal of this investigation was establishing a new simple and sensitive method that could be used in analysis of biological samples. The method was validated and successfully applied for determination of atorvastatin (acid and lactone forms) and its metabolites in plasma.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma",
volume = "18",
number = "3",
pages = "2469-2482",
doi = "10.3390/molecules18032469"
}

Crevar-Sakač, M., Vujić, Z., Brborić, J., Kuntić, V.,& Uskoković-Marković, S.. (2013). An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma. in Molecules
MDPI, Basel., 18(3), 2469-2482.
https://doi.org/10.3390/molecules18032469

Crevar-Sakač M, Vujić Z, Brborić J, Kuntić V, Uskoković-Marković S. An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma. in Molecules. 2013;18(3):2469-2482.
doi:10.3390/molecules18032469 .

Crevar-Sakač, Milkica, Vujić, Zorica, Brborić, Jasmina, Kuntić, Vesna, Uskoković-Marković, Snežana, "An Improved HPLC Method with the Aid of a Chemometric Protocol: Simultaneous Determination of Atorvastatin and Its Metabolites in Plasma" in Molecules, 18, no. 3 (2013):2469-2482,
https://doi.org/10.3390/molecules18032469 . .

TY  - JOUR
AU  - Vujić, Zorica
AU  - Crevar, Milkica
AU  - Obradović, Vladimir
AU  - Kuntić, Vesna
AU  - Uskoković-Marković, Snežana
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1160
AB  - A rapid and simple liquid chromatographic method with UV detection has been developed for the determination of hydrochlorothiazide (HCTZ), cilazapril (CL) and its active metabolite cilazaprilat (CLT) in urine. Sample preparation for urine consisted of solid-phase extraction using styrene-divinylbenzene (SDB-2) cartridges. The chromatographic system was a Zorbax Eclipse XDB-C-18 column with a mixture of methanol and 10 mM phosphate buffer, pH 2.3 with gradient (20 to 60% of methanol) as mobile phase at a flow rate of 1.0 mL min(-1). The detection was performed at the wavelength of 206 nm. Enalapril maleat was used as an internal standard. The detector response was linear in the range of 2.4-30.0, 1.6-15.0 and 1.8-20.0 mu g mL(-1) for HCTZ, CL and CLT, respectively. LOQ was determined to be 2.4, 1.6 and 1.8 mu g mL(-1) for HCTZ, CL and CLT, respectively. Both intra- and inter-day precision were within acceptable limits. The method has been applied to urine samples obtained from three hypertensive patients after intake of HCTZ and CL therapeutic dose.
PB  - Springer Heidelberg, Heidelberg
T2  - Chromatographia
T1  - Simultaneous Determination of Hydrochlorothiazide, Cilazapril and Its Active Metabolite Cilazaprilat in Urine by Gradient RP-LC
VL  - 70
IS  - 7-8
SP  - 1221
EP  - 1225
DO  - 10.1365/s10337-009-1286-6
ER  - 

@article{
author = "Vujić, Zorica and Crevar, Milkica and Obradović, Vladimir and Kuntić, Vesna and Uskoković-Marković, Snežana",
year = "2009",
abstract = "A rapid and simple liquid chromatographic method with UV detection has been developed for the determination of hydrochlorothiazide (HCTZ), cilazapril (CL) and its active metabolite cilazaprilat (CLT) in urine. Sample preparation for urine consisted of solid-phase extraction using styrene-divinylbenzene (SDB-2) cartridges. The chromatographic system was a Zorbax Eclipse XDB-C-18 column with a mixture of methanol and 10 mM phosphate buffer, pH 2.3 with gradient (20 to 60% of methanol) as mobile phase at a flow rate of 1.0 mL min(-1). The detection was performed at the wavelength of 206 nm. Enalapril maleat was used as an internal standard. The detector response was linear in the range of 2.4-30.0, 1.6-15.0 and 1.8-20.0 mu g mL(-1) for HCTZ, CL and CLT, respectively. LOQ was determined to be 2.4, 1.6 and 1.8 mu g mL(-1) for HCTZ, CL and CLT, respectively. Both intra- and inter-day precision were within acceptable limits. The method has been applied to urine samples obtained from three hypertensive patients after intake of HCTZ and CL therapeutic dose.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Chromatographia",
title = "Simultaneous Determination of Hydrochlorothiazide, Cilazapril and Its Active Metabolite Cilazaprilat in Urine by Gradient RP-LC",
volume = "70",
number = "7-8",
pages = "1221-1225",
doi = "10.1365/s10337-009-1286-6"
}

Vujić, Z., Crevar, M., Obradović, V., Kuntić, V.,& Uskoković-Marković, S.. (2009). Simultaneous Determination of Hydrochlorothiazide, Cilazapril and Its Active Metabolite Cilazaprilat in Urine by Gradient RP-LC. in Chromatographia
Springer Heidelberg, Heidelberg., 70(7-8), 1221-1225.
https://doi.org/10.1365/s10337-009-1286-6

Vujić Z, Crevar M, Obradović V, Kuntić V, Uskoković-Marković S. Simultaneous Determination of Hydrochlorothiazide, Cilazapril and Its Active Metabolite Cilazaprilat in Urine by Gradient RP-LC. in Chromatographia. 2009;70(7-8):1221-1225.
doi:10.1365/s10337-009-1286-6 .

Vujić, Zorica, Crevar, Milkica, Obradović, Vladimir, Kuntić, Vesna, Uskoković-Marković, Snežana, "Simultaneous Determination of Hydrochlorothiazide, Cilazapril and Its Active Metabolite Cilazaprilat in Urine by Gradient RP-LC" in Chromatographia, 70, no. 7-8 (2009):1221-1225,
https://doi.org/10.1365/s10337-009-1286-6 . .

TY  - JOUR
AU  - Crevar, Milkica
AU  - Ivković, Branka
AU  - Vladimirov, Sote
AU  - Kuntić, Vesna
AU  - Vujić, Zorica
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1064
AB  - Paracetamol, analgoantipyretic and anti-inflammatory drug, is available in numerous pharmaceutical formulations in common combination with caffeine and some other drug substances. p-aminophenol is paracatamol's process-related impurity that also may be present in formulations containing paracetamol. This paper presents a RP-HPLC method for simultaneous determination of caffeine, paracetamol and p-aminophenol, using chromatographic system Hewlett Packard 1100 series. In defining optimal RP-HPLC chromatographic conditions for the separation of these three compounds, experimental design was applied. Completely separation was achieved using Zorbax Extend C18 column (150 mm x 4.6 mm, 5 mu m), with mobile phase consisting of methanol-phosphate buffer pH 6 (20:80 v/v), flow rate of 1 ml/min, and column temperature of 30 degrees C. UV detection was performed at 230 nm.
PB  - Slovensko Kemijsko Drustvo, Ljubljana
T2  - Acta Chimica Slovenica
T1  - Statistical Optimization of Reverse Phase High Performance Liquid Chromatography for the Analysis of Caffeine Paracetamol and its Degradation Product p-aminophenol
VL  - 55
IS  - 3
SP  - 665
EP  - 670
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1064
ER  - 

@article{
author = "Crevar, Milkica and Ivković, Branka and Vladimirov, Sote and Kuntić, Vesna and Vujić, Zorica",
year = "2008",
abstract = "Paracetamol, analgoantipyretic and anti-inflammatory drug, is available in numerous pharmaceutical formulations in common combination with caffeine and some other drug substances. p-aminophenol is paracatamol's process-related impurity that also may be present in formulations containing paracetamol. This paper presents a RP-HPLC method for simultaneous determination of caffeine, paracetamol and p-aminophenol, using chromatographic system Hewlett Packard 1100 series. In defining optimal RP-HPLC chromatographic conditions for the separation of these three compounds, experimental design was applied. Completely separation was achieved using Zorbax Extend C18 column (150 mm x 4.6 mm, 5 mu m), with mobile phase consisting of methanol-phosphate buffer pH 6 (20:80 v/v), flow rate of 1 ml/min, and column temperature of 30 degrees C. UV detection was performed at 230 nm.",
publisher = "Slovensko Kemijsko Drustvo, Ljubljana",
journal = "Acta Chimica Slovenica",
title = "Statistical Optimization of Reverse Phase High Performance Liquid Chromatography for the Analysis of Caffeine Paracetamol and its Degradation Product p-aminophenol",
volume = "55",
number = "3",
pages = "665-670",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1064"
}

Crevar, M., Ivković, B., Vladimirov, S., Kuntić, V.,& Vujić, Z.. (2008). Statistical Optimization of Reverse Phase High Performance Liquid Chromatography for the Analysis of Caffeine Paracetamol and its Degradation Product p-aminophenol. in Acta Chimica Slovenica
Slovensko Kemijsko Drustvo, Ljubljana., 55(3), 665-670.
https://hdl.handle.net/21.15107/rcub_farfar_1064

Crevar M, Ivković B, Vladimirov S, Kuntić V, Vujić Z. Statistical Optimization of Reverse Phase High Performance Liquid Chromatography for the Analysis of Caffeine Paracetamol and its Degradation Product p-aminophenol. in Acta Chimica Slovenica. 2008;55(3):665-670.
https://hdl.handle.net/21.15107/rcub_farfar_1064 .

Crevar, Milkica, Ivković, Branka, Vladimirov, Sote, Kuntić, Vesna, Vujić, Zorica, "Statistical Optimization of Reverse Phase High Performance Liquid Chromatography for the Analysis of Caffeine Paracetamol and its Degradation Product p-aminophenol" in Acta Chimica Slovenica, 55, no. 3 (2008):665-670,
https://hdl.handle.net/21.15107/rcub_farfar_1064 .

TY  - JOUR
AU  - Vujić, Zorica
AU  - Crevar, Milkica
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/954
AB  - Depression constitutes an international health problem. It is estimated that 320 million people worldwide are clinically depressed. Effective antidepressant treatments have been available for more than 40 years. Although modern antidepressants lack many of the side-effects and toxicity of the first generation tricyclics and monoamine oxidase inhibitors, their efficiency has not been substantially improved comparing to older agents. Unfortunately, the modern drug discovery technologies of combinatorial chemistry and throughput screening are based on relatively simple in vitro assays and lack pre-clinical model of depression make this research difficult. Most antidepressants require additional time to achieve therapeutic effects and there is a certain population of patients resistant to current therapies which means that etiology of depression is too complex. Coming research should clarify true depression mechanism and identify new targets of the third antidepressants generation. Anxiety is a normal emotion and essential part of response to stressful and threatening stimuli. At present, a numerous drugs with various mechanism of action are available for pharmacoterapy of anxiety disorders. The benzodiazepines represent the most important drugs in the treatment of anxiety. In addition to their anxiolytic properties, benzodiazepines possess sedative, hypnotic, anticonvulsant and other effects but side effects also-upon prolonged administration they produce withdrawal symptoms and dependency. Research has shown that cholecystokinin and corticotrophin-releasing factor are important neurotransmiters and may have role in the mediation of anxiety. Neuropeptide Y has shown an anxiolytic effect in several animal models. CCK, CRF and neuropeptid Y receptor agonists and antagonists are targets of new anxiolitic drugs.
AB  - Anksioznost je normalna emocionalna reakcija na preteći ili stresni stimulans. U farmakoterapiji ove bolesti koristi se veliki broj lekova različitog mehanizma delovanja od kojih su benzodiazepini najvažniji. Benzodiazepini, pored anksiolitičkog poseduju sedativni, hipnotički, antikonvulzivni i druge efekte ali posle duže upotrebe razvija se tolerancija, dovode do zavisnosti i često su predmet zloupotrebe. Novija istraživanja su pokazala da, pored serotonina i noradrenalina i drugi neurotransmiteri kao što su holecistokinin (CCK) i oslobađajući faktor za kortikotropin (CRF) imaju značajnu ulogu u anksioznosti. Neuropeptid Y (NPY) takođe pokazuje anksiolitički efekat na životinjama. Agonisti i antagonisti receptora holecistokinina, oslobađajućeg faktora za kortikotropin i neuropeptida Y su cilj sinteze novih anksiolitika.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Antidepressants and anxiolyitic design trends
T1  - Trendovi u dizajniranju antidepresiva i anksiolitika
VL  - 57
IS  - 1-2
SP  - 24
EP  - 49
UR  - https://hdl.handle.net/21.15107/rcub_farfar_954
ER  - 

@article{
author = "Vujić, Zorica and Crevar, Milkica",
year = "2007",
abstract = "Depression constitutes an international health problem. It is estimated that 320 million people worldwide are clinically depressed. Effective antidepressant treatments have been available for more than 40 years. Although modern antidepressants lack many of the side-effects and toxicity of the first generation tricyclics and monoamine oxidase inhibitors, their efficiency has not been substantially improved comparing to older agents. Unfortunately, the modern drug discovery technologies of combinatorial chemistry and throughput screening are based on relatively simple in vitro assays and lack pre-clinical model of depression make this research difficult. Most antidepressants require additional time to achieve therapeutic effects and there is a certain population of patients resistant to current therapies which means that etiology of depression is too complex. Coming research should clarify true depression mechanism and identify new targets of the third antidepressants generation. Anxiety is a normal emotion and essential part of response to stressful and threatening stimuli. At present, a numerous drugs with various mechanism of action are available for pharmacoterapy of anxiety disorders. The benzodiazepines represent the most important drugs in the treatment of anxiety. In addition to their anxiolytic properties, benzodiazepines possess sedative, hypnotic, anticonvulsant and other effects but side effects also-upon prolonged administration they produce withdrawal symptoms and dependency. Research has shown that cholecystokinin and corticotrophin-releasing factor are important neurotransmiters and may have role in the mediation of anxiety. Neuropeptide Y has shown an anxiolytic effect in several animal models. CCK, CRF and neuropeptid Y receptor agonists and antagonists are targets of new anxiolitic drugs., Anksioznost je normalna emocionalna reakcija na preteći ili stresni stimulans. U farmakoterapiji ove bolesti koristi se veliki broj lekova različitog mehanizma delovanja od kojih su benzodiazepini najvažniji. Benzodiazepini, pored anksiolitičkog poseduju sedativni, hipnotički, antikonvulzivni i druge efekte ali posle duže upotrebe razvija se tolerancija, dovode do zavisnosti i često su predmet zloupotrebe. Novija istraživanja su pokazala da, pored serotonina i noradrenalina i drugi neurotransmiteri kao što su holecistokinin (CCK) i oslobađajući faktor za kortikotropin (CRF) imaju značajnu ulogu u anksioznosti. Neuropeptid Y (NPY) takođe pokazuje anksiolitički efekat na životinjama. Agonisti i antagonisti receptora holecistokinina, oslobađajućeg faktora za kortikotropin i neuropeptida Y su cilj sinteze novih anksiolitika.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Antidepressants and anxiolyitic design trends, Trendovi u dizajniranju antidepresiva i anksiolitika",
volume = "57",
number = "1-2",
pages = "24-49",
url = "https://hdl.handle.net/21.15107/rcub_farfar_954"
}

Vujić, Z.,& Crevar, M.. (2007). Antidepressants and anxiolyitic design trends. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 57(1-2), 24-49.
https://hdl.handle.net/21.15107/rcub_farfar_954

Vujić Z, Crevar M. Antidepressants and anxiolyitic design trends. in Arhiv za farmaciju. 2007;57(1-2):24-49.
https://hdl.handle.net/21.15107/rcub_farfar_954 .

Vujić, Zorica, Crevar, Milkica, "Antidepressants and anxiolyitic design trends" in Arhiv za farmaciju, 57, no. 1-2 (2007):24-49,
https://hdl.handle.net/21.15107/rcub_farfar_954 .

TY  - CONF
AU  - Crevar, Milkica
AU  - Ivković, Branka
AU  - Vladimirov, S.
AU  - Vujić, Zorica
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/678
PB  - Savez farmaceutskih udruženja Srbije, Beograd
C3  - Arhiv za farmaciju
T1  - Statistical optimization of reverse phase high performance liquid chromatography for the analysis of caffeine, paracetamole and its degradation product P-aminophenole
T1  - Statistička optimizačija reverzno fazne visokoefikasne tečne hromatografije za analizu kofeina, paracetamola i njegovog degradacionog proizvoda P-aminofenola
VL  - 56
IS  - 5
SP  - 734
EP  - 735
UR  - https://hdl.handle.net/21.15107/rcub_farfar_678
ER  - 

@conference{
author = "Crevar, Milkica and Ivković, Branka and Vladimirov, S. and Vujić, Zorica",
year = "2006",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Statistical optimization of reverse phase high performance liquid chromatography for the analysis of caffeine, paracetamole and its degradation product P-aminophenole, Statistička optimizačija reverzno fazne visokoefikasne tečne hromatografije za analizu kofeina, paracetamola i njegovog degradacionog proizvoda P-aminofenola",
volume = "56",
number = "5",
pages = "734-735",
url = "https://hdl.handle.net/21.15107/rcub_farfar_678"
}

Crevar, M., Ivković, B., Vladimirov, S.,& Vujić, Z.. (2006). Statistical optimization of reverse phase high performance liquid chromatography for the analysis of caffeine, paracetamole and its degradation product P-aminophenole. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 56(5), 734-735.
https://hdl.handle.net/21.15107/rcub_farfar_678

Crevar M, Ivković B, Vladimirov S, Vujić Z. Statistical optimization of reverse phase high performance liquid chromatography for the analysis of caffeine, paracetamole and its degradation product P-aminophenole. in Arhiv za farmaciju. 2006;56(5):734-735.
https://hdl.handle.net/21.15107/rcub_farfar_678 .

Crevar, Milkica, Ivković, Branka, Vladimirov, S., Vujić, Zorica, "Statistical optimization of reverse phase high performance liquid chromatography for the analysis of caffeine, paracetamole and its degradation product P-aminophenole" in Arhiv za farmaciju, 56, no. 5 (2006):734-735,
https://hdl.handle.net/21.15107/rcub_farfar_678 .