Kilibarda, Vesna

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4675a520-9aed-46d9-a560-bfb260ddd71d
  • Kilibarda, Vesna (19)
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Author's Bibliography

Rise of Pregabalin Poisoning and Abuse Cases in Serbia: A Ten-Year Retrospective Study

Antunović, Marko; Vučinić, Slavica; Kotur-Stevuljević, Jelena; Krstić, Kristijan; Jović-Stošić, Jasmina; Kilibarda, Vesna; Perković-Vukčević, Nataša; Đorđević, Snežana

(Dove Medical Press Ltd, 2023)

TY  - JOUR
AU  - Antunović, Marko
AU  - Vučinić, Slavica
AU  - Kotur-Stevuljević, Jelena
AU  - Krstić, Kristijan
AU  - Jović-Stošić, Jasmina
AU  - Kilibarda, Vesna
AU  - Perković-Vukčević, Nataša
AU  - Đorđević, Snežana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4699
AB  - Purpose: The aim of this study was to analyze data on gabapentinoid-related attendances to the National Poison Control Center of Serbia (NPCC), particularly abuse cases; to estimate its changes and to compare it with trends in national consumption rates of these drugs. We also aimed to analyze the main characteristics of the study population and to investigate the major clinical effects in poisoned patients. Patients and Methods: This is a retrospective study of patients admitted to the NPCC for acute poisoning involving gabapentinoids from 1 May 2012 to 1 October 2022. Results: There were 357 (95.5%) pregabalin-related and 17 (4.5%) gabapentin-related poisoning cases in 302 patients. Abuse of pregabalin was detected in 27.8% (84/302), while gabapentin abuse occurred in 0.7% (2/302) of all patients. A steady increase in rates of pregabalin poisoning and abuse cases strongly correlated with the increase in overall consumption of this drug, while there were no significant changes in rates of gabapentin consumption, poisoning and abuse rate during the study period. Most patients who abused pregabalin pregabalin were males (84.5%) and the median age was 26 years (range: 15–45 years). Almost 60% of patients who abused pregabalin (48/84) belonged to the migrant population. Co-ingestions occurred in 89.4% of pregabalin-related cases (319/357), resulting in more severe poisoning. The most often co-ingested drugs were benzodiazepines and among them clonazepam was detected in the largest number of cases. Conclusion: The poisoning and abuse cases involving pregabalin are on the rise in Serbia, which coincided with an increase in its overall consumption during the study period. Isolated pregabalin ingestions resulted in mild poisoning, although severe symptoms such as coma and bradycardia were recorded. When prescribing pregabalin to patients at risk of abuse caution is needed. Strengthening the measures for dispensing of pregabalin may reduce the risks associated with its abuse.
PB  - Dove Medical Press Ltd
T2  - International Journal of General Medicine
T1  - Rise of Pregabalin Poisoning and Abuse Cases in Serbia: A Ten-Year Retrospective Study
VL  - 16
VL  - 16
SP  - 1239
SP  - 1250
EP  - 1250
EP  - 1250
DO  - 10.2147/IJGM.S405616
ER  - 
@article{
author = "Antunović, Marko and Vučinić, Slavica and Kotur-Stevuljević, Jelena and Krstić, Kristijan and Jović-Stošić, Jasmina and Kilibarda, Vesna and Perković-Vukčević, Nataša and Đorđević, Snežana",
year = "2023",
abstract = "Purpose: The aim of this study was to analyze data on gabapentinoid-related attendances to the National Poison Control Center of Serbia (NPCC), particularly abuse cases; to estimate its changes and to compare it with trends in national consumption rates of these drugs. We also aimed to analyze the main characteristics of the study population and to investigate the major clinical effects in poisoned patients. Patients and Methods: This is a retrospective study of patients admitted to the NPCC for acute poisoning involving gabapentinoids from 1 May 2012 to 1 October 2022. Results: There were 357 (95.5%) pregabalin-related and 17 (4.5%) gabapentin-related poisoning cases in 302 patients. Abuse of pregabalin was detected in 27.8% (84/302), while gabapentin abuse occurred in 0.7% (2/302) of all patients. A steady increase in rates of pregabalin poisoning and abuse cases strongly correlated with the increase in overall consumption of this drug, while there were no significant changes in rates of gabapentin consumption, poisoning and abuse rate during the study period. Most patients who abused pregabalin pregabalin were males (84.5%) and the median age was 26 years (range: 15–45 years). Almost 60% of patients who abused pregabalin (48/84) belonged to the migrant population. Co-ingestions occurred in 89.4% of pregabalin-related cases (319/357), resulting in more severe poisoning. The most often co-ingested drugs were benzodiazepines and among them clonazepam was detected in the largest number of cases. Conclusion: The poisoning and abuse cases involving pregabalin are on the rise in Serbia, which coincided with an increase in its overall consumption during the study period. Isolated pregabalin ingestions resulted in mild poisoning, although severe symptoms such as coma and bradycardia were recorded. When prescribing pregabalin to patients at risk of abuse caution is needed. Strengthening the measures for dispensing of pregabalin may reduce the risks associated with its abuse.",
publisher = "Dove Medical Press Ltd",
journal = "International Journal of General Medicine",
title = "Rise of Pregabalin Poisoning and Abuse Cases in Serbia: A Ten-Year Retrospective Study",
volume = "16, 16",
pages = "1239-1250-1250-1250",
doi = "10.2147/IJGM.S405616"
}
Antunović, M., Vučinić, S., Kotur-Stevuljević, J., Krstić, K., Jović-Stošić, J., Kilibarda, V., Perković-Vukčević, N.,& Đorđević, S.. (2023). Rise of Pregabalin Poisoning and Abuse Cases in Serbia: A Ten-Year Retrospective Study. in International Journal of General Medicine
Dove Medical Press Ltd., 16, 1239-1250.
https://doi.org/10.2147/IJGM.S405616
Antunović M, Vučinić S, Kotur-Stevuljević J, Krstić K, Jović-Stošić J, Kilibarda V, Perković-Vukčević N, Đorđević S. Rise of Pregabalin Poisoning and Abuse Cases in Serbia: A Ten-Year Retrospective Study. in International Journal of General Medicine. 2023;16:1239-1250.
doi:10.2147/IJGM.S405616 .
Antunović, Marko, Vučinić, Slavica, Kotur-Stevuljević, Jelena, Krstić, Kristijan, Jović-Stošić, Jasmina, Kilibarda, Vesna, Perković-Vukčević, Nataša, Đorđević, Snežana, "Rise of Pregabalin Poisoning and Abuse Cases in Serbia: A Ten-Year Retrospective Study" in International Journal of General Medicine, 16 (2023):1239-1250,
https://doi.org/10.2147/IJGM.S405616 . .
2
4
2

Rise of Pregabalin Poisoning and Abuse Cases in Serbia: A Ten-Year Retrospective Study

Antunović, Marko; Vučinić, Slavica; Kotur-Stevuljević, Jelena; Krstić, Kristijan; Jović-Stošić, Jasmina; Kilibarda, Vesna; Perković-Vukčević, Nataša; Đorđević, Snežana

(Dove Medical Press Ltd, 2023)

TY  - JOUR
AU  - Antunović, Marko
AU  - Vučinić, Slavica
AU  - Kotur-Stevuljević, Jelena
AU  - Krstić, Kristijan
AU  - Jović-Stošić, Jasmina
AU  - Kilibarda, Vesna
AU  - Perković-Vukčević, Nataša
AU  - Đorđević, Snežana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5415
AB  - Purpose: The aim of this study was to analyze data on gabapentinoid-related attendances to the National Poison Control Center of Serbia (NPCC), particularly abuse cases; to estimate its changes and to compare it with trends in national consumption rates of these drugs. We also aimed to analyze the main characteristics of the study population and to investigate the major clinical effects in poisoned patients. Patients and Methods: This is a retrospective study of patients admitted to the NPCC for acute poisoning involving gabapentinoids from 1 May 2012 to 1 October 2022. Results: There were 357 (95.5%) pregabalin-related and 17 (4.5%) gabapentin-related poisoning cases in 302 patients. Abuse of pregabalin was detected in 27.8% (84/302), while gabapentin abuse occurred in 0.7% (2/302) of all patients. A steady increase in rates of pregabalin poisoning and abuse cases strongly correlated with the increase in overall consumption of this drug, while there were no significant changes in rates of gabapentin consumption, poisoning and abuse rate during the study period. Most patients who abused pregabalin pregabalin were males (84.5%) and the median age was 26 years (range: 15–45 years). Almost 60% of patients who abused pregabalin (48/84) belonged to the migrant population. Co-ingestions occurred in 89.4% of pregabalin-related cases (319/357), resulting in more severe poisoning. The most often co-ingested drugs were benzodiazepines and among them clonazepam was detected in the largest number of cases. Conclusion: The poisoning and abuse cases involving pregabalin are on the rise in Serbia, which coincided with an increase in its overall consumption during the study period. Isolated pregabalin ingestions resulted in mild poisoning, although severe symptoms such as coma and bradycardia were recorded. When prescribing pregabalin to patients at risk of abuse caution is needed. Strengthening the measures for dispensing of pregabalin may reduce the risks associated with its abuse.
PB  - Dove Medical Press Ltd
T2  - International Journal of General Medicine
T1  - Rise of Pregabalin Poisoning and Abuse Cases in Serbia: A Ten-Year Retrospective Study
VL  - 16
SP  - 1239
EP  - 1250
DO  - 10.2147/IJGM.S405616
ER  - 
@article{
author = "Antunović, Marko and Vučinić, Slavica and Kotur-Stevuljević, Jelena and Krstić, Kristijan and Jović-Stošić, Jasmina and Kilibarda, Vesna and Perković-Vukčević, Nataša and Đorđević, Snežana",
year = "2023",
abstract = "Purpose: The aim of this study was to analyze data on gabapentinoid-related attendances to the National Poison Control Center of Serbia (NPCC), particularly abuse cases; to estimate its changes and to compare it with trends in national consumption rates of these drugs. We also aimed to analyze the main characteristics of the study population and to investigate the major clinical effects in poisoned patients. Patients and Methods: This is a retrospective study of patients admitted to the NPCC for acute poisoning involving gabapentinoids from 1 May 2012 to 1 October 2022. Results: There were 357 (95.5%) pregabalin-related and 17 (4.5%) gabapentin-related poisoning cases in 302 patients. Abuse of pregabalin was detected in 27.8% (84/302), while gabapentin abuse occurred in 0.7% (2/302) of all patients. A steady increase in rates of pregabalin poisoning and abuse cases strongly correlated with the increase in overall consumption of this drug, while there were no significant changes in rates of gabapentin consumption, poisoning and abuse rate during the study period. Most patients who abused pregabalin pregabalin were males (84.5%) and the median age was 26 years (range: 15–45 years). Almost 60% of patients who abused pregabalin (48/84) belonged to the migrant population. Co-ingestions occurred in 89.4% of pregabalin-related cases (319/357), resulting in more severe poisoning. The most often co-ingested drugs were benzodiazepines and among them clonazepam was detected in the largest number of cases. Conclusion: The poisoning and abuse cases involving pregabalin are on the rise in Serbia, which coincided with an increase in its overall consumption during the study period. Isolated pregabalin ingestions resulted in mild poisoning, although severe symptoms such as coma and bradycardia were recorded. When prescribing pregabalin to patients at risk of abuse caution is needed. Strengthening the measures for dispensing of pregabalin may reduce the risks associated with its abuse.",
publisher = "Dove Medical Press Ltd",
journal = "International Journal of General Medicine",
title = "Rise of Pregabalin Poisoning and Abuse Cases in Serbia: A Ten-Year Retrospective Study",
volume = "16",
pages = "1239-1250",
doi = "10.2147/IJGM.S405616"
}
Antunović, M., Vučinić, S., Kotur-Stevuljević, J., Krstić, K., Jović-Stošić, J., Kilibarda, V., Perković-Vukčević, N.,& Đorđević, S.. (2023). Rise of Pregabalin Poisoning and Abuse Cases in Serbia: A Ten-Year Retrospective Study. in International Journal of General Medicine
Dove Medical Press Ltd., 16, 1239-1250.
https://doi.org/10.2147/IJGM.S405616
Antunović M, Vučinić S, Kotur-Stevuljević J, Krstić K, Jović-Stošić J, Kilibarda V, Perković-Vukčević N, Đorđević S. Rise of Pregabalin Poisoning and Abuse Cases in Serbia: A Ten-Year Retrospective Study. in International Journal of General Medicine. 2023;16:1239-1250.
doi:10.2147/IJGM.S405616 .
Antunović, Marko, Vučinić, Slavica, Kotur-Stevuljević, Jelena, Krstić, Kristijan, Jović-Stošić, Jasmina, Kilibarda, Vesna, Perković-Vukčević, Nataša, Đorđević, Snežana, "Rise of Pregabalin Poisoning and Abuse Cases in Serbia: A Ten-Year Retrospective Study" in International Journal of General Medicine, 16 (2023):1239-1250,
https://doi.org/10.2147/IJGM.S405616 . .
2
4
2

Development and validation of a rapid and simple UPLC/MS method for quantification of therapeutic and toxic valproic acid concentrations in patient plasma

Antunović, Marko; Đorđević, Snežana; Kilibarda, Vesna; Džudović, Jelena; Repić, Aleksandra; Bulat, Zorica

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - JOUR
AU  - Antunović, Marko
AU  - Đorđević, Snežana
AU  - Kilibarda, Vesna
AU  - Džudović, Jelena
AU  - Repić, Aleksandra
AU  - Bulat, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4498
AB  - Valproic acid (VPA) is antiepileptic drug with a long history of clinical use,
increasingly applied in the treatment of various diseases (bipolar disorder, migraine
prophylaxis, etc). Due to significant inter-individual differences VPA concentration is often
measured in the purpose of therapeutic drug monitoring (TDM) (1). Acute poisonings with
this drug represent a significant problem. According to the American Association of Poison
Control Centers, there has been VPA poisoning incidence increase in the last 20 years.
Reports from the National Poison Control Center in Belgrade list VPA as one of the three
most common causes of antiepileptic drugs intoxications (2). This paper aimed to develop a
modern analytical method for VPA quantification in patient plasma. UPLC/MS method with
fast and simple sample preparation has been validated. After protein precipitation, VPA was
extracted from 100 μL plasma using HLB cartridges. Caprylic acid solution was used as
internal standard. Chromatographic separation was achieved on C18 column (1.8 μm, 2.1 X
150 mm) with gradient elution at constant mobile phase flow. Good peak resolution was
achieved (Rt VPA - 4.73 min, Rt ISTD - 4.94 min). Validation was performed according European
Medicines Agency recommendations. Based on statistical analysism it was shown that the
method is precise, accurate, specific, sensitive and linearity is confirmed in a wide range of
concentrations (1-250 mg / L). Advantages of this method are simple preparation procedure
from a small amount of sample, without prior derivatization and short duration of analysis,
which fully satisfies the needs of TDM and urgent toxicological analyses.
AB  - Valproinska kiselina (VK) je lek iz grupe antiepileptika sa dugom istorijom kliničke
upotrebe, koji se, osim u terapiji epilepsije, poslednjih decenija sve više koristi u terapiji
različitih bolesti (bipolarni poremećaj, profilaksa migrene itd). Zbog značajnih
interindividualnih varijacija, koncentracija VK se često određuje u svrhe terapijskog praćenja
leka (TDM – Therapeutic Drug Monitoring) (1). S druge strane, akutna trovanja ovim lekom
predstavljaju značajan problem. Prema podacima Američkih centara za kontrolu trovanja
došlo je do povećanja incidence trovanja VK u poslednjih 20 godina, dok izveštaji
Nacionalnog centra za kontrolu trovanja u Beogradu navode VK kao jedan od tri najčešća
uzročnika trovanja kada su u pitanju intoksikacije antiepilepticima (2). Cilj ovoga rada je
razvoj savremene analitičke metode za određivanje koncentracije VK u plazmi pacijenata.
Validovana je UPLC/MS metoda koja podrazumeva brzu i jednostavnu pripremu uzorka.
Nakon precipitacije proteina, izvršena je ekstrakcija iz 100 μL plazme uz pomoć HLB
kertridža. Kao interni standard korišćen je rastvor kaprilne kiseline. Hromatografsko
razdvajanje je postignuto na C18 koloni (1,8 μm, 2,1 X 150 mm) gradijentnim eluiranjem pri
konstantnom protoku mobilne faze. Postignuta je dobra rezolucija pikova (Rt VK - 4,73 min,
Rt ISTD - 4,94 min). Validacija je izvedena prema preporukama Evropske agencije za lekove, a
na osnovu statističke analize je pokazano da je metoda precizna, tačna, specifična, osetljiva i
potvrđena je linearnost u širokom opsegu koncentracija (1-250 mg/L). Prednosti ove
metode su jednostavan način pripreme iz male količine uzorka, bez prethodne derivatizacije,
i kratko vreme trajanja analize, što u potpunosti zadovoljava potrebe TDM-a i urgentnih
toksikoloških analiza.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
T2  - Arhiv za farmaciju
T1  - Development and validation of a rapid and simple UPLC/MS method for quantification of therapeutic and toxic valproic acid concentrations in patient plasma
T1  - Razvoj i validacija brze i jednostavne UPLC/MS metode za određivanje terapijskih i toksičnih koncentracija valproinske kiseline u plazmi pacijenata
VL  - 72
IS  - 4 suplement
SP  - S215
EP  - S216
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4498
ER  - 
@article{
author = "Antunović, Marko and Đorđević, Snežana and Kilibarda, Vesna and Džudović, Jelena and Repić, Aleksandra and Bulat, Zorica",
year = "2022",
abstract = "Valproic acid (VPA) is antiepileptic drug with a long history of clinical use,
increasingly applied in the treatment of various diseases (bipolar disorder, migraine
prophylaxis, etc). Due to significant inter-individual differences VPA concentration is often
measured in the purpose of therapeutic drug monitoring (TDM) (1). Acute poisonings with
this drug represent a significant problem. According to the American Association of Poison
Control Centers, there has been VPA poisoning incidence increase in the last 20 years.
Reports from the National Poison Control Center in Belgrade list VPA as one of the three
most common causes of antiepileptic drugs intoxications (2). This paper aimed to develop a
modern analytical method for VPA quantification in patient plasma. UPLC/MS method with
fast and simple sample preparation has been validated. After protein precipitation, VPA was
extracted from 100 μL plasma using HLB cartridges. Caprylic acid solution was used as
internal standard. Chromatographic separation was achieved on C18 column (1.8 μm, 2.1 X
150 mm) with gradient elution at constant mobile phase flow. Good peak resolution was
achieved (Rt VPA - 4.73 min, Rt ISTD - 4.94 min). Validation was performed according European
Medicines Agency recommendations. Based on statistical analysism it was shown that the
method is precise, accurate, specific, sensitive and linearity is confirmed in a wide range of
concentrations (1-250 mg / L). Advantages of this method are simple preparation procedure
from a small amount of sample, without prior derivatization and short duration of analysis,
which fully satisfies the needs of TDM and urgent toxicological analyses., Valproinska kiselina (VK) je lek iz grupe antiepileptika sa dugom istorijom kliničke
upotrebe, koji se, osim u terapiji epilepsije, poslednjih decenija sve više koristi u terapiji
različitih bolesti (bipolarni poremećaj, profilaksa migrene itd). Zbog značajnih
interindividualnih varijacija, koncentracija VK se često određuje u svrhe terapijskog praćenja
leka (TDM – Therapeutic Drug Monitoring) (1). S druge strane, akutna trovanja ovim lekom
predstavljaju značajan problem. Prema podacima Američkih centara za kontrolu trovanja
došlo je do povećanja incidence trovanja VK u poslednjih 20 godina, dok izveštaji
Nacionalnog centra za kontrolu trovanja u Beogradu navode VK kao jedan od tri najčešća
uzročnika trovanja kada su u pitanju intoksikacije antiepilepticima (2). Cilj ovoga rada je
razvoj savremene analitičke metode za određivanje koncentracije VK u plazmi pacijenata.
Validovana je UPLC/MS metoda koja podrazumeva brzu i jednostavnu pripremu uzorka.
Nakon precipitacije proteina, izvršena je ekstrakcija iz 100 μL plazme uz pomoć HLB
kertridža. Kao interni standard korišćen je rastvor kaprilne kiseline. Hromatografsko
razdvajanje je postignuto na C18 koloni (1,8 μm, 2,1 X 150 mm) gradijentnim eluiranjem pri
konstantnom protoku mobilne faze. Postignuta je dobra rezolucija pikova (Rt VK - 4,73 min,
Rt ISTD - 4,94 min). Validacija je izvedena prema preporukama Evropske agencije za lekove, a
na osnovu statističke analize je pokazano da je metoda precizna, tačna, specifična, osetljiva i
potvrđena je linearnost u širokom opsegu koncentracija (1-250 mg/L). Prednosti ove
metode su jednostavan način pripreme iz male količine uzorka, bez prethodne derivatizacije,
i kratko vreme trajanja analize, što u potpunosti zadovoljava potrebe TDM-a i urgentnih
toksikoloških analiza.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Development and validation of a rapid and simple UPLC/MS method for quantification of therapeutic and toxic valproic acid concentrations in patient plasma, Razvoj i validacija brze i jednostavne UPLC/MS metode za određivanje terapijskih i toksičnih koncentracija valproinske kiseline u plazmi pacijenata",
volume = "72",
number = "4 suplement",
pages = "S215-S216",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4498"
}
Antunović, M., Đorđević, S., Kilibarda, V., Džudović, J., Repić, A.,& Bulat, Z.. (2022). Development and validation of a rapid and simple UPLC/MS method for quantification of therapeutic and toxic valproic acid concentrations in patient plasma. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S215-S216.
https://hdl.handle.net/21.15107/rcub_farfar_4498
Antunović M, Đorđević S, Kilibarda V, Džudović J, Repić A, Bulat Z. Development and validation of a rapid and simple UPLC/MS method for quantification of therapeutic and toxic valproic acid concentrations in patient plasma. in Arhiv za farmaciju. 2022;72(4 suplement):S215-S216.
https://hdl.handle.net/21.15107/rcub_farfar_4498 .
Antunović, Marko, Đorđević, Snežana, Kilibarda, Vesna, Džudović, Jelena, Repić, Aleksandra, Bulat, Zorica, "Development and validation of a rapid and simple UPLC/MS method for quantification of therapeutic and toxic valproic acid concentrations in patient plasma" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S215-S216,
https://hdl.handle.net/21.15107/rcub_farfar_4498 .

Clinical and analytical experience of the National Poison Control Centre with synthetic cannabinoids

Vučinić, Slavica; Kilibarda, Vesna; Đorđević, Snežana; Đorđević, Dragana; Perković-Vukcević, Nataša; Vuković-Ercegović, Gordana; Antonijević, Biljana; Ćurčić, Marijana; Antonijević, Evica; Brajković, Gordana

(Inst Medical Research & Occupational Health, Zagreb, 2018)

TY  - JOUR
AU  - Vučinić, Slavica
AU  - Kilibarda, Vesna
AU  - Đorđević, Snežana
AU  - Đorđević, Dragana
AU  - Perković-Vukcević, Nataša
AU  - Vuković-Ercegović, Gordana
AU  - Antonijević, Biljana
AU  - Ćurčić, Marijana
AU  - Antonijević, Evica
AU  - Brajković, Gordana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3196
AB  - A rising number of patients are being treated for overdosing with new psychoactive substances (NPS) available at the illegal drug market in Serbia. The aim of this study was to report clinical and analytical experience of the National Poison Control Centre of Serbia (NPCC) with synthetic cannabinoids (SCs) and point to the NPS available at the illegal drug market in our country. From January 2013 to December 2016, 58 patients (aged between 14 and 25) were treated for the effects of synthetic cannabinoids at the NPCC. Tachycardia was established in 53, mydriasis in 31, somnolence, nausea. vomiting, and agitation in 16, dizziness in 10, disorientation in 9, dyspnoea and chest pain in 4, and loss of consciousness, pallor, paraesthesia, muscle twitches, and short-term memory impairment in 2 patients. After receiving symptomatic and supportive treatment in the emergency ward, all patients had fully recovered within 8 h and were discharged shortly afterwards. Another part of the study was focused on the analysis of the products known under their local street names as "Biljni tamjan" (herbal incense), "Beli slez", and "Rainbow Special" and the analysis of urine sampled from the patients with gas chromatography - mass spectrometry, and high performance liquid chromatography. The detected synthetic cannabinoids were AB-PINACA, JWH-018, JWH-122, JWH-210, 5F-AKB48, and MDMB-CHMICA in herbal products and AB-FUBINACA, AB-CHMINACA, and MDMB-CHIvIICA in the urine samples. Our findings have shown the great capacity of NPCC to I) monitor NPS abuse in Serbia, II) reliably detect SCs in illicit products and biological samples, and III) clinically manage the adverse effects in their users. Future commitments of the NPCC will include systematic collection of relevant data on SCs and their adverse effects, detection of changes in purity and composition of the controlled NPS-based products, and raising the public awareness of NPS to improve the effectiveness of the national Early Warning System.
PB  - Inst Medical Research & Occupational Health, Zagreb
T2  - Arhiv za higijenu rada i toksikologiju - Archives of Industrial Hygiene and Toxicology
T1  - Clinical and analytical experience of the National Poison Control Centre with synthetic cannabinoids
VL  - 69
IS  - 2
SP  - 178
EP  - 185
DO  - 10.2478/aiht-2018-69-3096
ER  - 
@article{
author = "Vučinić, Slavica and Kilibarda, Vesna and Đorđević, Snežana and Đorđević, Dragana and Perković-Vukcević, Nataša and Vuković-Ercegović, Gordana and Antonijević, Biljana and Ćurčić, Marijana and Antonijević, Evica and Brajković, Gordana",
year = "2018",
abstract = "A rising number of patients are being treated for overdosing with new psychoactive substances (NPS) available at the illegal drug market in Serbia. The aim of this study was to report clinical and analytical experience of the National Poison Control Centre of Serbia (NPCC) with synthetic cannabinoids (SCs) and point to the NPS available at the illegal drug market in our country. From January 2013 to December 2016, 58 patients (aged between 14 and 25) were treated for the effects of synthetic cannabinoids at the NPCC. Tachycardia was established in 53, mydriasis in 31, somnolence, nausea. vomiting, and agitation in 16, dizziness in 10, disorientation in 9, dyspnoea and chest pain in 4, and loss of consciousness, pallor, paraesthesia, muscle twitches, and short-term memory impairment in 2 patients. After receiving symptomatic and supportive treatment in the emergency ward, all patients had fully recovered within 8 h and were discharged shortly afterwards. Another part of the study was focused on the analysis of the products known under their local street names as "Biljni tamjan" (herbal incense), "Beli slez", and "Rainbow Special" and the analysis of urine sampled from the patients with gas chromatography - mass spectrometry, and high performance liquid chromatography. The detected synthetic cannabinoids were AB-PINACA, JWH-018, JWH-122, JWH-210, 5F-AKB48, and MDMB-CHMICA in herbal products and AB-FUBINACA, AB-CHMINACA, and MDMB-CHIvIICA in the urine samples. Our findings have shown the great capacity of NPCC to I) monitor NPS abuse in Serbia, II) reliably detect SCs in illicit products and biological samples, and III) clinically manage the adverse effects in their users. Future commitments of the NPCC will include systematic collection of relevant data on SCs and their adverse effects, detection of changes in purity and composition of the controlled NPS-based products, and raising the public awareness of NPS to improve the effectiveness of the national Early Warning System.",
publisher = "Inst Medical Research & Occupational Health, Zagreb",
journal = "Arhiv za higijenu rada i toksikologiju - Archives of Industrial Hygiene and Toxicology",
title = "Clinical and analytical experience of the National Poison Control Centre with synthetic cannabinoids",
volume = "69",
number = "2",
pages = "178-185",
doi = "10.2478/aiht-2018-69-3096"
}
Vučinić, S., Kilibarda, V., Đorđević, S., Đorđević, D., Perković-Vukcević, N., Vuković-Ercegović, G., Antonijević, B., Ćurčić, M., Antonijević, E.,& Brajković, G.. (2018). Clinical and analytical experience of the National Poison Control Centre with synthetic cannabinoids. in Arhiv za higijenu rada i toksikologiju - Archives of Industrial Hygiene and Toxicology
Inst Medical Research & Occupational Health, Zagreb., 69(2), 178-185.
https://doi.org/10.2478/aiht-2018-69-3096
Vučinić S, Kilibarda V, Đorđević S, Đorđević D, Perković-Vukcević N, Vuković-Ercegović G, Antonijević B, Ćurčić M, Antonijević E, Brajković G. Clinical and analytical experience of the National Poison Control Centre with synthetic cannabinoids. in Arhiv za higijenu rada i toksikologiju - Archives of Industrial Hygiene and Toxicology. 2018;69(2):178-185.
doi:10.2478/aiht-2018-69-3096 .
Vučinić, Slavica, Kilibarda, Vesna, Đorđević, Snežana, Đorđević, Dragana, Perković-Vukcević, Nataša, Vuković-Ercegović, Gordana, Antonijević, Biljana, Ćurčić, Marijana, Antonijević, Evica, Brajković, Gordana, "Clinical and analytical experience of the National Poison Control Centre with synthetic cannabinoids" in Arhiv za higijenu rada i toksikologiju - Archives of Industrial Hygiene and Toxicology, 69, no. 2 (2018):178-185,
https://doi.org/10.2478/aiht-2018-69-3096 . .
11
6
11

Determination of JWH-210, JWH-122 and JWH-081 in urine by Liquid Chromatography Mass Spectrometric method

Brajković, Gordana; Jović-Stošić, Jasmina; Đorđević, Snežana; Kilibarda, Vesna; Ćurčić, Marijana; Radosavljević-Stevanović, Nataša; Brajković, Zorica; Vučinić, Slavica

(Elsevier Ireland Ltd, Clare, 2017)

TY  - CONF
AU  - Brajković, Gordana
AU  - Jović-Stošić, Jasmina
AU  - Đorđević, Snežana
AU  - Kilibarda, Vesna
AU  - Ćurčić, Marijana
AU  - Radosavljević-Stevanović, Nataša
AU  - Brajković, Zorica
AU  - Vučinić, Slavica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2890
PB  - Elsevier Ireland Ltd, Clare
C3  - Toxicology Letters
T1  - Determination of JWH-210, JWH-122 and JWH-081 in urine by Liquid Chromatography Mass Spectrometric method
VL  - 280
IS  - Supplement 1
SP  - S292
EP  - S292
DO  - 10.1016/j.toxlet.2017.07.820
ER  - 
@conference{
author = "Brajković, Gordana and Jović-Stošić, Jasmina and Đorđević, Snežana and Kilibarda, Vesna and Ćurčić, Marijana and Radosavljević-Stevanović, Nataša and Brajković, Zorica and Vučinić, Slavica",
year = "2017",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Toxicology Letters",
title = "Determination of JWH-210, JWH-122 and JWH-081 in urine by Liquid Chromatography Mass Spectrometric method",
volume = "280",
number = "Supplement 1",
pages = "S292-S292",
doi = "10.1016/j.toxlet.2017.07.820"
}
Brajković, G., Jović-Stošić, J., Đorđević, S., Kilibarda, V., Ćurčić, M., Radosavljević-Stevanović, N., Brajković, Z.,& Vučinić, S.. (2017). Determination of JWH-210, JWH-122 and JWH-081 in urine by Liquid Chromatography Mass Spectrometric method. in Toxicology Letters
Elsevier Ireland Ltd, Clare., 280(Supplement 1), S292-S292.
https://doi.org/10.1016/j.toxlet.2017.07.820
Brajković G, Jović-Stošić J, Đorđević S, Kilibarda V, Ćurčić M, Radosavljević-Stevanović N, Brajković Z, Vučinić S. Determination of JWH-210, JWH-122 and JWH-081 in urine by Liquid Chromatography Mass Spectrometric method. in Toxicology Letters. 2017;280(Supplement 1):S292-S292.
doi:10.1016/j.toxlet.2017.07.820 .
Brajković, Gordana, Jović-Stošić, Jasmina, Đorđević, Snežana, Kilibarda, Vesna, Ćurčić, Marijana, Radosavljević-Stevanović, Nataša, Brajković, Zorica, Vučinić, Slavica, "Determination of JWH-210, JWH-122 and JWH-081 in urine by Liquid Chromatography Mass Spectrometric method" in Toxicology Letters, 280, no. Supplement 1 (2017):S292-S292,
https://doi.org/10.1016/j.toxlet.2017.07.820 . .

Influence of decabrominated diphenyl ether on cadmium as oxidative stress inducer in kidney: Subacute oral study in rats

Ćurčić, Marijana; Antunović, Marko; Džoković, Maja; Janković, Saša; Milovanović, Vesna; Đorđević, Snežana; Kilibarda, Vesna; Vučinić, Slavica; Antonijević, Biljana

(Most Art doo, Beograd, 2016)

TY  - JOUR
AU  - Ćurčić, Marijana
AU  - Antunović, Marko
AU  - Džoković, Maja
AU  - Janković, Saša
AU  - Milovanović, Vesna
AU  - Đorđević, Snežana
AU  - Kilibarda, Vesna
AU  - Vučinić, Slavica
AU  - Antonijević, Biljana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2552
AB  - It is known that kidneys are target tissue for Cd toxicity but there is not enough literature data on kidney effects of BDE-209. Moreover, Cd as toxic metal and BDE-209 as organic halogenated pollutant can share similar mechanism of action like, oxidative stress which is already assumed. However, how will Cd act as prooxidant in presence of BDE-209 is still not investigated, therefore, the objective of this study was to assess this BDE-209 influence. Results of this study indicated slight decrease in MDA in rat's kidney homogenates after subacute exposure to Cd and/or BDE-209, while SOD activity was increased and content of -SH groups decreased. Based on dose-response assessment, BDE-209 did not influence Cd toxicity mediated by chosen oxidative stress parameters, namely the derived CEDL5 values were the same for single Cd and for Cd given in combination with the BDE-209. In conclusion, dynamic of oxidative process has influence on the parameters levels. Co-exposure with polybrominated organic pollutant did not influence Cd effects on oxidative stress parameters. Having in mind that this is pilot study, performed with only one dose of BDE-209, further investigations are necessary, including changes in dose ranges, duration of exposure etc. Moreover, results contributes to the issue of mixture toxicology even BDE-209 did not influenced oxidative stress as mechanism of Cd toxicity.
AB  - Poznato je da su bubrezi ciljni organ toksičnosti kadmijuma, ali je mnogo manje literaturnih podataka o toksičnim efektima BDE-209 na bubrege. Kadmijum, kao toksičan metal i BDE-209, kao organska halogenovana zagađujuća supstanca mogu imati sličan mehanizam dejstva posredovan oksidativnim stresom. Međutim, kako će Cd da deluje kao prooksidant u prisustvu BDE-209 još uvek nije proučavano, te je cilj ovog rada bio da se proceni uticaj BDE-209 na oksidativni stres posredovan kadmijumom. Rezultati ovog istraživanja ukazuju na blagi pad koncentracije MDA u homogenatima bubrega pacova nakon subakutne ekspozicije Cd i/ili BDE-209, dok se aktivnost SOD povećava i sadržaj - SH grupa smanjuje. Na osnovu procene odnosa doza-odgovor, BDE-209 nije imao uticaja na toksičnost Cd izazvanu posredstvom oksidativnog stresa (posmatrajući odabrane parametre). Potvrda je dobijena i iz izračunatih donjih granica pouzdanosti doze od 5% - CEDL5 jer su vrednosti su bile iste za sam Cd i Cd primenjen u kombinaciji sa BDE-209. Može se zaključiti da dinamika oksidativnih procesa ima uticaj na vrednosti parametara oksidativnog stresa, da stoga istovremena ekspozicija Cd i polibromovanom organskom polutantu nije promenila uticaj samog Cd na parametre oksidativnog stresa. Imajući u vidu da je ovo pilot studija, izvršena sa samo jednom dozom BDE-209, potrebna su dalja istraživanja, uključujući i promene opsega doza, trajanje ekspozicije itd. Pored toga, rezultati ove studije doprinose tumačenju toksikologija smeša, iako BDE-209 nije imao uticaja na oksidativni stres kao mehanizam Cd toksičnosti za date uslove ekspozicije.
PB  - Most Art doo, Beograd
T2  - MD - Medical data
T1  - Influence of decabrominated diphenyl ether on cadmium as oxidative stress inducer in kidney: Subacute oral study in rats
T1  - Uticaj dekabromovanog difenil etra na toksičnost kadmijuma posredstvom oksidativnog stresa - subakutna oralna studija na pacovima
VL  - 8
IS  - 1
SP  - 17
EP  - 20
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2552
ER  - 
@article{
author = "Ćurčić, Marijana and Antunović, Marko and Džoković, Maja and Janković, Saša and Milovanović, Vesna and Đorđević, Snežana and Kilibarda, Vesna and Vučinić, Slavica and Antonijević, Biljana",
year = "2016",
abstract = "It is known that kidneys are target tissue for Cd toxicity but there is not enough literature data on kidney effects of BDE-209. Moreover, Cd as toxic metal and BDE-209 as organic halogenated pollutant can share similar mechanism of action like, oxidative stress which is already assumed. However, how will Cd act as prooxidant in presence of BDE-209 is still not investigated, therefore, the objective of this study was to assess this BDE-209 influence. Results of this study indicated slight decrease in MDA in rat's kidney homogenates after subacute exposure to Cd and/or BDE-209, while SOD activity was increased and content of -SH groups decreased. Based on dose-response assessment, BDE-209 did not influence Cd toxicity mediated by chosen oxidative stress parameters, namely the derived CEDL5 values were the same for single Cd and for Cd given in combination with the BDE-209. In conclusion, dynamic of oxidative process has influence on the parameters levels. Co-exposure with polybrominated organic pollutant did not influence Cd effects on oxidative stress parameters. Having in mind that this is pilot study, performed with only one dose of BDE-209, further investigations are necessary, including changes in dose ranges, duration of exposure etc. Moreover, results contributes to the issue of mixture toxicology even BDE-209 did not influenced oxidative stress as mechanism of Cd toxicity., Poznato je da su bubrezi ciljni organ toksičnosti kadmijuma, ali je mnogo manje literaturnih podataka o toksičnim efektima BDE-209 na bubrege. Kadmijum, kao toksičan metal i BDE-209, kao organska halogenovana zagađujuća supstanca mogu imati sličan mehanizam dejstva posredovan oksidativnim stresom. Međutim, kako će Cd da deluje kao prooksidant u prisustvu BDE-209 još uvek nije proučavano, te je cilj ovog rada bio da se proceni uticaj BDE-209 na oksidativni stres posredovan kadmijumom. Rezultati ovog istraživanja ukazuju na blagi pad koncentracije MDA u homogenatima bubrega pacova nakon subakutne ekspozicije Cd i/ili BDE-209, dok se aktivnost SOD povećava i sadržaj - SH grupa smanjuje. Na osnovu procene odnosa doza-odgovor, BDE-209 nije imao uticaja na toksičnost Cd izazvanu posredstvom oksidativnog stresa (posmatrajući odabrane parametre). Potvrda je dobijena i iz izračunatih donjih granica pouzdanosti doze od 5% - CEDL5 jer su vrednosti su bile iste za sam Cd i Cd primenjen u kombinaciji sa BDE-209. Može se zaključiti da dinamika oksidativnih procesa ima uticaj na vrednosti parametara oksidativnog stresa, da stoga istovremena ekspozicija Cd i polibromovanom organskom polutantu nije promenila uticaj samog Cd na parametre oksidativnog stresa. Imajući u vidu da je ovo pilot studija, izvršena sa samo jednom dozom BDE-209, potrebna su dalja istraživanja, uključujući i promene opsega doza, trajanje ekspozicije itd. Pored toga, rezultati ove studije doprinose tumačenju toksikologija smeša, iako BDE-209 nije imao uticaja na oksidativni stres kao mehanizam Cd toksičnosti za date uslove ekspozicije.",
publisher = "Most Art doo, Beograd",
journal = "MD - Medical data",
title = "Influence of decabrominated diphenyl ether on cadmium as oxidative stress inducer in kidney: Subacute oral study in rats, Uticaj dekabromovanog difenil etra na toksičnost kadmijuma posredstvom oksidativnog stresa - subakutna oralna studija na pacovima",
volume = "8",
number = "1",
pages = "17-20",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2552"
}
Ćurčić, M., Antunović, M., Džoković, M., Janković, S., Milovanović, V., Đorđević, S., Kilibarda, V., Vučinić, S.,& Antonijević, B.. (2016). Influence of decabrominated diphenyl ether on cadmium as oxidative stress inducer in kidney: Subacute oral study in rats. in MD - Medical data
Most Art doo, Beograd., 8(1), 17-20.
https://hdl.handle.net/21.15107/rcub_farfar_2552
Ćurčić M, Antunović M, Džoković M, Janković S, Milovanović V, Đorđević S, Kilibarda V, Vučinić S, Antonijević B. Influence of decabrominated diphenyl ether on cadmium as oxidative stress inducer in kidney: Subacute oral study in rats. in MD - Medical data. 2016;8(1):17-20.
https://hdl.handle.net/21.15107/rcub_farfar_2552 .
Ćurčić, Marijana, Antunović, Marko, Džoković, Maja, Janković, Saša, Milovanović, Vesna, Đorđević, Snežana, Kilibarda, Vesna, Vučinić, Slavica, Antonijević, Biljana, "Influence of decabrominated diphenyl ether on cadmium as oxidative stress inducer in kidney: Subacute oral study in rats" in MD - Medical data, 8, no. 1 (2016):17-20,
https://hdl.handle.net/21.15107/rcub_farfar_2552 .

Abusing of psychoactive substance in 2015-National Poison Control Center Serbia Data

Đorđević, S.; Antunović, M.; Kilibarda, Vesna; Brajković, Gordana; Ćurčić, Marijana; Jović-Stošić, Jasmina; Vučinić, Slavica

(Elsevier Ireland Ltd, Clare, 2016)

TY  - CONF
AU  - Đorđević, S.
AU  - Antunović, M.
AU  - Kilibarda, Vesna
AU  - Brajković, Gordana
AU  - Ćurčić, Marijana
AU  - Jović-Stošić, Jasmina
AU  - Vučinić, Slavica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2644
PB  - Elsevier Ireland Ltd, Clare
C3  - Toxicology Letters
T1  - Abusing of psychoactive substance in 2015-National Poison Control Center Serbia Data
VL  - 258
SP  - S104
EP  - S105
DO  - 10.1016/j.toxlet.2016.06.1440
ER  - 
@conference{
author = "Đorđević, S. and Antunović, M. and Kilibarda, Vesna and Brajković, Gordana and Ćurčić, Marijana and Jović-Stošić, Jasmina and Vučinić, Slavica",
year = "2016",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Toxicology Letters",
title = "Abusing of psychoactive substance in 2015-National Poison Control Center Serbia Data",
volume = "258",
pages = "S104-S105",
doi = "10.1016/j.toxlet.2016.06.1440"
}
Đorđević, S., Antunović, M., Kilibarda, V., Brajković, G., Ćurčić, M., Jović-Stošić, J.,& Vučinić, S.. (2016). Abusing of psychoactive substance in 2015-National Poison Control Center Serbia Data. in Toxicology Letters
Elsevier Ireland Ltd, Clare., 258, S104-S105.
https://doi.org/10.1016/j.toxlet.2016.06.1440
Đorđević S, Antunović M, Kilibarda V, Brajković G, Ćurčić M, Jović-Stošić J, Vučinić S. Abusing of psychoactive substance in 2015-National Poison Control Center Serbia Data. in Toxicology Letters. 2016;258:S104-S105.
doi:10.1016/j.toxlet.2016.06.1440 .
Đorđević, S., Antunović, M., Kilibarda, Vesna, Brajković, Gordana, Ćurčić, Marijana, Jović-Stošić, Jasmina, Vučinić, Slavica, "Abusing of psychoactive substance in 2015-National Poison Control Center Serbia Data" in Toxicology Letters, 258 (2016):S104-S105,
https://doi.org/10.1016/j.toxlet.2016.06.1440 . .

Relationship of hepatotoxicity and the target tissue dose of decabrominated diphenyl ether in subacutely exposed Wistar rats

Ćurčić, Marijana; Tanasković, Slađana; Stanković, Sanja; Janković, Saša; Antunović, Marko; Đorđević, Snežana; Kilibarda, Vesna; Vučinić, Slavica; Antonijević, Biljana

(Vojnomedicinska akademija - Institut za naučne informacije, Beograd, 2015)

TY  - JOUR
AU  - Ćurčić, Marijana
AU  - Tanasković, Slađana
AU  - Stanković, Sanja
AU  - Janković, Saša
AU  - Antunović, Marko
AU  - Đorđević, Snežana
AU  - Kilibarda, Vesna
AU  - Vučinić, Slavica
AU  - Antonijević, Biljana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2474
AB  - Background/Aim. Based on numerous studies in animals, the most prominent toxic effects of decabrominated di-phenyl ether (BDE-209) are observed in the liver, thyroid hormone homeostasis, reproductive and nervous systems. BDE-209 exhibits its toxic effects partly through the aryl hydrocarbon (Ah) receptor and consequent induction of hepatic microsomal enzymes. The aim of this study was to assess the hepatotoxic effect vs target tissue dose of BDE-209 in the subacutely orally exposed Wistar rats. Methods. Effects were examined on male Wistar rats, weighing 200-240 g, exposed to doses of 1,000, 2,000 or 4,000 mg BDE-209/kg body weight (bw)/day by gavage during 28 days. Animals were treated according to the decision of the Ethics Committee of the Military Medical Academy, No 9667-1/2011. Evaluation of the hepatotoxic effect was based on: relative liver weight water and food intake, biochemical parameters of liver function [aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gama glutamyl transferase (γ-GT)], and oxidative stress parameters in liver homogenates [malondialdehiyde (MDA), superoxide dismutase (SOD), -SH] and morphological and pathohistological changes in the liver. For the assessment of internal dose - response relationship, lower confidence limit of Benchmark dose (BMDL) of 5% or 10% i.e. BMDL5 or BMDL10, were calculated using PROAST software. Results. After the application of 1,000, 2,000 or 4,000 mg BDE-209/kg bw/day, the concentrations of BDE-209 measured in liver were 0.269, 0.569 and 0.859 mg/kg of liver wet weight, (ww) respectively. Internal doses correlated with external (r = 0.972; p  lt  0.05) according to equation: internal dose (mg BDE-209/kg of liver ww) = 0.0002 ' external dose (mg/kg bw/day) + 0.0622. Hepato-toxicity was demonstrated based on significant increase in AST and γ-GT activities and the degree of histopathological changes. The lowest BMDL5 of 0.07228 mg BDE-209/kg of liver ww, correlating to external dose of 39 mg/kg/day, indicated the increase of AST activity as the most sensitive biomarker of BDE-209 hepatotoxicity in subacutely ex-posed rats. Conclusion. The results of the present work add up to the issue of BDE-209 toxicity profile with a focus on relationship between internal dose and hepatotoxicity. Critical internal dose for the effect on AST of 0.07 mg/kg of liver ww, corresponding to external dose of 39 mg/kg/day, is the lowest dose ever observed among the studies on BDE-209 hepatotoxicity. For the persistent sub-stances with low absorption rate such as BDE-209, critical effect based on internal dose in majority of cases is considered as more precisely defined than the effect established based on external dose, particularly.
AB  - Uvod/Cilj. Prema podacima iz brojnih studija na životinjama, dekabromovani difeniletar (BDE-209) najznačajnije toksične efekte ispoljava na jetri, homeostazi hormona štitaste žlezde, reproduktivnom i nervnom sistemu. BDE-209 ispoljava toksične efekte delom preko receptora za aromatične ugljovodonike (Ah) i posledične indukcije mikrozomalnih enzima jetre. Cilj rada bio je procena hepatotoksičnog efekta u odnosu na dozu BDE-209 u ciljnom tkivu kod subakutno oralno eksponovanih Wistar pacova. Metode. Efekti su ispitivani na mužjacima Wistar pacova, mase 200-240 g, koji su putem oralne sonde primali doze od 1 000, 2 000 ili 4 000 mg BDE-209/kg telesne mase (tm) dan, tokom 28 dana. Životinje su tretirane u skladu sa odlukom Etičkog komiteta Vojnomedicinske akademije u Beogradu br. 9667-1/2011. Procena hepatotoksičnih efekata bazirana je na merenju relativne mase jetre, unosa vode i hrane, biohemijskih parametara funkcije jetre [aspartat aminotransferaza (AST), alanin amino-transferaza (ALT), alkalna fosfataza (ALP), gama glutamil transferaza (γ-GT)], parametara oksidativnog stresa u homogenatima jetre [malondialdehid (MDA), superoksid dizmutaza (SOD), -SH)] i morfoloških i histoloških promena na jetri. Za procenu odnosa interna doza - odgovor izračunavana je donja granica pouzdanosti granične Benchmark doze (BMDL) od 5% (BMDL5) ili 10% (BMDL10) primenom PROAST softvera. Rezultati. Koncentracije BDE-209 iznosile su 0,269, 0,569 i 0,859 mg/kg jetre nakon aplikacije 1 000, 2 000, odnosno 4 000 mg BDE-209/kg tm/dan. Interna doza u našoj studiji korelisala je sa eksternom dozom prema jednačini: interna doza (mg BDE-209/kg jetre) = 0,0002 ' eksterna doza (mg/kg tm/dan) + 0,0622 (r = 0,972; p  lt  0,05). Hepatotoksičnost je potvrđena na osnovu nalaza o povećanju aktivnosti enzima AST i γ-GT, kao i stepena patohistološkog oštećenja jetre. Najniža BMDL5 u eksperimentu od 0,07228 mg BDE-209/kg jetre, koja koreliše sa eksternom dozom od 39 mg/kg tm/dan izračunata je za aktivnost AST i ukazuje na to da je aktivnost AST ujedno i najosetljiviji biomarker hepatotoksičnosti BDE-209 kod subakutno eksponovanih pacova. Zaključak. Rezultati prezentovane studije daju doprinos pitanju toksikološkog profila BDE-209 sa fokusom na odnos između interne doze i hepatotoksičnih efekata. Kritična interna doza za efekat na AST od 0,07 mg/kg jetre, koja koreliše sa eksternom dozom od 39 mg/kg tm/dan, jeste ujedno i najniža kritična doza do sada definisana za hepatotoksične efekte BDE-209. Kritičan efekat koji se bazira na dozi u ciljnom tkivu u većini slučajeva može se smatrati preciznije definisanim od kritičnog efekta definisanog na bazi oralno primenjene doze, naročito za nedegradabilne supstance sa niskim stepenom apsorpcije, kao što je BDE-209.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Relationship of hepatotoxicity and the target tissue dose of decabrominated diphenyl ether in subacutely exposed Wistar rats
T1  - Odnos hepatotoksičnosti i doze dekabromovanog difeniletra u ciljnom tkivu kod subakutno izloženih Wistar pacova
VL  - 72
IS  - 5
SP  - 405
EP  - 413
DO  - 10.2298/VSP1505405C
ER  - 
@article{
author = "Ćurčić, Marijana and Tanasković, Slađana and Stanković, Sanja and Janković, Saša and Antunović, Marko and Đorđević, Snežana and Kilibarda, Vesna and Vučinić, Slavica and Antonijević, Biljana",
year = "2015",
abstract = "Background/Aim. Based on numerous studies in animals, the most prominent toxic effects of decabrominated di-phenyl ether (BDE-209) are observed in the liver, thyroid hormone homeostasis, reproductive and nervous systems. BDE-209 exhibits its toxic effects partly through the aryl hydrocarbon (Ah) receptor and consequent induction of hepatic microsomal enzymes. The aim of this study was to assess the hepatotoxic effect vs target tissue dose of BDE-209 in the subacutely orally exposed Wistar rats. Methods. Effects were examined on male Wistar rats, weighing 200-240 g, exposed to doses of 1,000, 2,000 or 4,000 mg BDE-209/kg body weight (bw)/day by gavage during 28 days. Animals were treated according to the decision of the Ethics Committee of the Military Medical Academy, No 9667-1/2011. Evaluation of the hepatotoxic effect was based on: relative liver weight water and food intake, biochemical parameters of liver function [aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gama glutamyl transferase (γ-GT)], and oxidative stress parameters in liver homogenates [malondialdehiyde (MDA), superoxide dismutase (SOD), -SH] and morphological and pathohistological changes in the liver. For the assessment of internal dose - response relationship, lower confidence limit of Benchmark dose (BMDL) of 5% or 10% i.e. BMDL5 or BMDL10, were calculated using PROAST software. Results. After the application of 1,000, 2,000 or 4,000 mg BDE-209/kg bw/day, the concentrations of BDE-209 measured in liver were 0.269, 0.569 and 0.859 mg/kg of liver wet weight, (ww) respectively. Internal doses correlated with external (r = 0.972; p  lt  0.05) according to equation: internal dose (mg BDE-209/kg of liver ww) = 0.0002 ' external dose (mg/kg bw/day) + 0.0622. Hepato-toxicity was demonstrated based on significant increase in AST and γ-GT activities and the degree of histopathological changes. The lowest BMDL5 of 0.07228 mg BDE-209/kg of liver ww, correlating to external dose of 39 mg/kg/day, indicated the increase of AST activity as the most sensitive biomarker of BDE-209 hepatotoxicity in subacutely ex-posed rats. Conclusion. The results of the present work add up to the issue of BDE-209 toxicity profile with a focus on relationship between internal dose and hepatotoxicity. Critical internal dose for the effect on AST of 0.07 mg/kg of liver ww, corresponding to external dose of 39 mg/kg/day, is the lowest dose ever observed among the studies on BDE-209 hepatotoxicity. For the persistent sub-stances with low absorption rate such as BDE-209, critical effect based on internal dose in majority of cases is considered as more precisely defined than the effect established based on external dose, particularly., Uvod/Cilj. Prema podacima iz brojnih studija na životinjama, dekabromovani difeniletar (BDE-209) najznačajnije toksične efekte ispoljava na jetri, homeostazi hormona štitaste žlezde, reproduktivnom i nervnom sistemu. BDE-209 ispoljava toksične efekte delom preko receptora za aromatične ugljovodonike (Ah) i posledične indukcije mikrozomalnih enzima jetre. Cilj rada bio je procena hepatotoksičnog efekta u odnosu na dozu BDE-209 u ciljnom tkivu kod subakutno oralno eksponovanih Wistar pacova. Metode. Efekti su ispitivani na mužjacima Wistar pacova, mase 200-240 g, koji su putem oralne sonde primali doze od 1 000, 2 000 ili 4 000 mg BDE-209/kg telesne mase (tm) dan, tokom 28 dana. Životinje su tretirane u skladu sa odlukom Etičkog komiteta Vojnomedicinske akademije u Beogradu br. 9667-1/2011. Procena hepatotoksičnih efekata bazirana je na merenju relativne mase jetre, unosa vode i hrane, biohemijskih parametara funkcije jetre [aspartat aminotransferaza (AST), alanin amino-transferaza (ALT), alkalna fosfataza (ALP), gama glutamil transferaza (γ-GT)], parametara oksidativnog stresa u homogenatima jetre [malondialdehid (MDA), superoksid dizmutaza (SOD), -SH)] i morfoloških i histoloških promena na jetri. Za procenu odnosa interna doza - odgovor izračunavana je donja granica pouzdanosti granične Benchmark doze (BMDL) od 5% (BMDL5) ili 10% (BMDL10) primenom PROAST softvera. Rezultati. Koncentracije BDE-209 iznosile su 0,269, 0,569 i 0,859 mg/kg jetre nakon aplikacije 1 000, 2 000, odnosno 4 000 mg BDE-209/kg tm/dan. Interna doza u našoj studiji korelisala je sa eksternom dozom prema jednačini: interna doza (mg BDE-209/kg jetre) = 0,0002 ' eksterna doza (mg/kg tm/dan) + 0,0622 (r = 0,972; p  lt  0,05). Hepatotoksičnost je potvrđena na osnovu nalaza o povećanju aktivnosti enzima AST i γ-GT, kao i stepena patohistološkog oštećenja jetre. Najniža BMDL5 u eksperimentu od 0,07228 mg BDE-209/kg jetre, koja koreliše sa eksternom dozom od 39 mg/kg tm/dan izračunata je za aktivnost AST i ukazuje na to da je aktivnost AST ujedno i najosetljiviji biomarker hepatotoksičnosti BDE-209 kod subakutno eksponovanih pacova. Zaključak. Rezultati prezentovane studije daju doprinos pitanju toksikološkog profila BDE-209 sa fokusom na odnos između interne doze i hepatotoksičnih efekata. Kritična interna doza za efekat na AST od 0,07 mg/kg jetre, koja koreliše sa eksternom dozom od 39 mg/kg tm/dan, jeste ujedno i najniža kritična doza do sada definisana za hepatotoksične efekte BDE-209. Kritičan efekat koji se bazira na dozi u ciljnom tkivu u većini slučajeva može se smatrati preciznije definisanim od kritičnog efekta definisanog na bazi oralno primenjene doze, naročito za nedegradabilne supstance sa niskim stepenom apsorpcije, kao što je BDE-209.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Relationship of hepatotoxicity and the target tissue dose of decabrominated diphenyl ether in subacutely exposed Wistar rats, Odnos hepatotoksičnosti i doze dekabromovanog difeniletra u ciljnom tkivu kod subakutno izloženih Wistar pacova",
volume = "72",
number = "5",
pages = "405-413",
doi = "10.2298/VSP1505405C"
}
Ćurčić, M., Tanasković, S., Stanković, S., Janković, S., Antunović, M., Đorđević, S., Kilibarda, V., Vučinić, S.,& Antonijević, B.. (2015). Relationship of hepatotoxicity and the target tissue dose of decabrominated diphenyl ether in subacutely exposed Wistar rats. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 72(5), 405-413.
https://doi.org/10.2298/VSP1505405C
Ćurčić M, Tanasković S, Stanković S, Janković S, Antunović M, Đorđević S, Kilibarda V, Vučinić S, Antonijević B. Relationship of hepatotoxicity and the target tissue dose of decabrominated diphenyl ether in subacutely exposed Wistar rats. in Vojnosanitetski pregled. 2015;72(5):405-413.
doi:10.2298/VSP1505405C .
Ćurčić, Marijana, Tanasković, Slađana, Stanković, Sanja, Janković, Saša, Antunović, Marko, Đorđević, Snežana, Kilibarda, Vesna, Vučinić, Slavica, Antonijević, Biljana, "Relationship of hepatotoxicity and the target tissue dose of decabrominated diphenyl ether in subacutely exposed Wistar rats" in Vojnosanitetski pregled, 72, no. 5 (2015):405-413,
https://doi.org/10.2298/VSP1505405C . .
6
3
7

Dramatic increase of "Herbal incense" and "Sharp Blueberry" users: Clinical patterns, analytical data and the impact to regulatory actions

Vučinić, Slavica; Kilibarda, Vesna; Jović-Stošić, Jasmina; Jovanović, M.; Antonijević, Biljana; Antonijević, Evica; Brajković, Gordana

(Elsevier Ireland Ltd, Clare, 2015)

TY  - CONF
AU  - Vučinić, Slavica
AU  - Kilibarda, Vesna
AU  - Jović-Stošić, Jasmina
AU  - Jovanović, M.
AU  - Antonijević, Biljana
AU  - Antonijević, Evica
AU  - Brajković, Gordana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2371
PB  - Elsevier Ireland Ltd, Clare
C3  - Toxicology Letters
T1  - Dramatic increase of "Herbal incense" and "Sharp Blueberry" users: Clinical patterns, analytical data and the impact to regulatory actions
VL  - 238
IS  - 2, Supplement
SP  - S145
EP  - S145
DO  - 10.1016/j.toxlet.2015.08.456
ER  - 
@conference{
author = "Vučinić, Slavica and Kilibarda, Vesna and Jović-Stošić, Jasmina and Jovanović, M. and Antonijević, Biljana and Antonijević, Evica and Brajković, Gordana",
year = "2015",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Toxicology Letters",
title = "Dramatic increase of "Herbal incense" and "Sharp Blueberry" users: Clinical patterns, analytical data and the impact to regulatory actions",
volume = "238",
number = "2, Supplement",
pages = "S145-S145",
doi = "10.1016/j.toxlet.2015.08.456"
}
Vučinić, S., Kilibarda, V., Jović-Stošić, J., Jovanović, M., Antonijević, B., Antonijević, E.,& Brajković, G.. (2015). Dramatic increase of "Herbal incense" and "Sharp Blueberry" users: Clinical patterns, analytical data and the impact to regulatory actions. in Toxicology Letters
Elsevier Ireland Ltd, Clare., 238(2, Supplement), S145-S145.
https://doi.org/10.1016/j.toxlet.2015.08.456
Vučinić S, Kilibarda V, Jović-Stošić J, Jovanović M, Antonijević B, Antonijević E, Brajković G. Dramatic increase of "Herbal incense" and "Sharp Blueberry" users: Clinical patterns, analytical data and the impact to regulatory actions. in Toxicology Letters. 2015;238(2, Supplement):S145-S145.
doi:10.1016/j.toxlet.2015.08.456 .
Vučinić, Slavica, Kilibarda, Vesna, Jović-Stošić, Jasmina, Jovanović, M., Antonijević, Biljana, Antonijević, Evica, Brajković, Gordana, "Dramatic increase of "Herbal incense" and "Sharp Blueberry" users: Clinical patterns, analytical data and the impact to regulatory actions" in Toxicology Letters, 238, no. 2, Supplement (2015):S145-S145,
https://doi.org/10.1016/j.toxlet.2015.08.456 . .

Beta-lactam antibiotics use in intensive care units: The pathophysiological, pharmacokinetic, pharmacodynamic and pharmacoeconomic approach

Perić, Aneta; Šurbatović, Maja; Vezmar-Kovačević, Sandra; Antunović, Mirjana; Veljović, Milić; Krstić-Lečić, Ivana; Đorđević, Dragan; Kilibarda, Vesna; Zeba, Snježana; Dobrić, Silva

(Vojnomedicinska akademija - Institut za naučne informacije, Beograd, 2015)

TY  - JOUR
AU  - Perić, Aneta
AU  - Šurbatović, Maja
AU  - Vezmar-Kovačević, Sandra
AU  - Antunović, Mirjana
AU  - Veljović, Milić
AU  - Krstić-Lečić, Ivana
AU  - Đorđević, Dragan
AU  - Kilibarda, Vesna
AU  - Zeba, Snježana
AU  - Dobrić, Silva
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2473
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Beta-lactam antibiotics use in intensive care units: The pathophysiological, pharmacokinetic, pharmacodynamic and pharmacoeconomic approach
T1  - Upotreba beta-laktamskih antibiotika u jedinicama intenzivne terapije - patofiziološki, farmakokinetički, farmakodinamički i farmakoekonomski pristup
VL  - 72
IS  - 2
SP  - 175
EP  - 180
DO  - 10.2298/VSP1502175P
ER  - 
@article{
author = "Perić, Aneta and Šurbatović, Maja and Vezmar-Kovačević, Sandra and Antunović, Mirjana and Veljović, Milić and Krstić-Lečić, Ivana and Đorđević, Dragan and Kilibarda, Vesna and Zeba, Snježana and Dobrić, Silva",
year = "2015",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Beta-lactam antibiotics use in intensive care units: The pathophysiological, pharmacokinetic, pharmacodynamic and pharmacoeconomic approach, Upotreba beta-laktamskih antibiotika u jedinicama intenzivne terapije - patofiziološki, farmakokinetički, farmakodinamički i farmakoekonomski pristup",
volume = "72",
number = "2",
pages = "175-180",
doi = "10.2298/VSP1502175P"
}
Perić, A., Šurbatović, M., Vezmar-Kovačević, S., Antunović, M., Veljović, M., Krstić-Lečić, I., Đorđević, D., Kilibarda, V., Zeba, S.,& Dobrić, S.. (2015). Beta-lactam antibiotics use in intensive care units: The pathophysiological, pharmacokinetic, pharmacodynamic and pharmacoeconomic approach. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 72(2), 175-180.
https://doi.org/10.2298/VSP1502175P
Perić A, Šurbatović M, Vezmar-Kovačević S, Antunović M, Veljović M, Krstić-Lečić I, Đorđević D, Kilibarda V, Zeba S, Dobrić S. Beta-lactam antibiotics use in intensive care units: The pathophysiological, pharmacokinetic, pharmacodynamic and pharmacoeconomic approach. in Vojnosanitetski pregled. 2015;72(2):175-180.
doi:10.2298/VSP1502175P .
Perić, Aneta, Šurbatović, Maja, Vezmar-Kovačević, Sandra, Antunović, Mirjana, Veljović, Milić, Krstić-Lečić, Ivana, Đorđević, Dragan, Kilibarda, Vesna, Zeba, Snježana, Dobrić, Silva, "Beta-lactam antibiotics use in intensive care units: The pathophysiological, pharmacokinetic, pharmacodynamic and pharmacoeconomic approach" in Vojnosanitetski pregled, 72, no. 2 (2015):175-180,
https://doi.org/10.2298/VSP1502175P . .

Determination of morphine, codeine and 6-monoacetylmorphine in saliva of substance-abuse patients using HPLC/MS methods

Milovanović, Vesna; Ćirić, Biljana; Milenković, Jasna; Kilibarda, Vesna; Ćurčić, Marijana; Vučinić, Slavica; Antonijević, Biljana

(Vojnomedicinska akademija - Institut za naučne informacije, Beograd, 2012)

TY  - JOUR
AU  - Milovanović, Vesna
AU  - Ćirić, Biljana
AU  - Milenković, Jasna
AU  - Kilibarda, Vesna
AU  - Ćurčić, Marijana
AU  - Vučinić, Slavica
AU  - Antonijević, Biljana
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1830
AB  - Background/Aim. Saliva represents an alternative specimen for substances abuse determination in toxicology. Hence, the aim of this study was to optimize a method for saliva specimen preparation for heroin metabolites, morphine and 6-monoacetylmorphine (6-mam), and codeine determination by liquid chromatography-mass spectrometry (LC/MS), and to apply this method on saliva samples taken from the patients. Methods. Saliva specimen was prepared using liqiud/liquid extraction of morphine, codeine and 6- mam by mixture of chloroform and isopropanol (9 : 1; v/v). Extracts were analysed by HPLC/MS technique: separation column Waters Spherisorb® 5 μm, ODS2, 4.6 × 100 mm; mobile phase: ammonium acetate : acetonitile (80 : 20; v/v), mobile phase flow rate 0.3 mL/min; mass detection range: 100-400 m/z. Regression and correlation analyses were performed with the probalility level of 0.05. Concentrations of morphine, codeine and 6-mam were determined in saliva samples of the patients with 'opiates' in urine identified by the test strips. Results. Calibration for each analysed substance was done in the concentration range from 0.1 to 1 mg/L and the coefficient of correlation was R2 > 0.99. We obtained following calibration curves: y = 385531x + 14584; y = 398036x + 31542; and y = 524162x - 27105, for morphine, codeine and 6-mam, respectively. Recovery for morphine and codeine determination was 99%, while for 6- mam it was 94%. Limits of detection and quantification of a proposed method were 0.01 mg/L and 0.05 mg/L, respectively. Concentration of morphine in the saliva of the heroin users ranged between 0.54 and 5.82 mg/L, concentration of codeine between 0.05 and 5.33, and 6-mam between 0.01 and 0.68 mg/L. A statistically significant correlation between codeine and 6-mam concentrations was obtained. Conclusion. A proposed HPLC/MS method for morphine, codeine and 6-mam determination in saliva is accurate, simple, cheap and suitable for routine analysis and monitoring of heroin abuse.
AB  - Uvod/Cilj. Saliva predstavlja alternativni matriks za identifikaciju sredstava zloupotrebe. Cilj ovog rada bio je optimizacija metode pripreme uzorka salive i određivanja metabolita heroina, morfina i 6-monoacetilmorfina (6-mam), i kodeina liquid chromatography-mass spectrometry (LC/MS) metodom i provera metode u realnim uslovima kod heroinomana. Metode. Priprema uzoraka vršena je tečno-tečnom ekstrakcijom uz smešu hloroforma i izopropil alkohola u odnosu 9 : 1. Ekstrakti su analizirani tehnikom HPLC/MS: razdvajanje na koloni Waters Spherisorb® 5 μm, ODS2, 4,6 × 100 mm, vršeno je primenom mobilne faze amonijum-acetat : acetonitril u odnosu 80 : 20 pri protoku od 0,3 mL/min. Masena detekcija je vršena u opsegu masa od 100 do 400 m/z. Primenjene su regresiona i korelaciona analiza za nivo verovatnoće 0,05. Određivanje prisustva morfina, kodeina i 6-mam vršeno je u uzorcima salive kod osoba kod kojih je test trakama utvrđeno prisustvo 'opijata' u urinu. Rezultati. Kalibracija je vršena u opsegu koncentracija 0,1-1 mg/L sa koeficijentom determinacije R2 > 0,99. Dobijene su kalibracione krive: za morfin, y = 385531x + 14584; kodein, y = 398036x + 31542 i 6- monoacetilmorfin, y = 524162x - 27105. Recovery vrednosti za određivanje morfina i kodeina iznosile su 99%, a za 6-mam 94%. Limit detekcije predložene metode iznosio je 0,01 mg/L, a limit kvantifikacije 0,05 mg/L. U salivi uživalaca heroina koncentracija morfina kretala se u opsegu od 0,54 do 5,82 mg/L, kodeina od 0,05 do 5,33, a 6-mam od 0,01 do 0,68 mg/L i dobijena je statistički značajna korelacija između vrednosti za kodein i 6-mam. Zaključak. Predložena HPLC/MS metoda za određivanje sadržaja morfina, kodeina i 6-monoacetilmorfina u salivi je tačna, jednostavna, ekonomična i pogodna za rutinsku primenu, kao i za biomonitoring zloupotrebe heroina.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Determination of morphine, codeine and 6-monoacetylmorphine in saliva of substance-abuse patients using HPLC/MS methods
T1  - Određivanje morfina, kodeina i 6-monoacetilmorfina metodom HPLC/MS u salivi heroinskih zavisnika
VL  - 69
IS  - 2
SP  - 141
EP  - 146
DO  - 10.2298/VSP1202141M
ER  - 
@article{
author = "Milovanović, Vesna and Ćirić, Biljana and Milenković, Jasna and Kilibarda, Vesna and Ćurčić, Marijana and Vučinić, Slavica and Antonijević, Biljana",
year = "2012",
abstract = "Background/Aim. Saliva represents an alternative specimen for substances abuse determination in toxicology. Hence, the aim of this study was to optimize a method for saliva specimen preparation for heroin metabolites, morphine and 6-monoacetylmorphine (6-mam), and codeine determination by liquid chromatography-mass spectrometry (LC/MS), and to apply this method on saliva samples taken from the patients. Methods. Saliva specimen was prepared using liqiud/liquid extraction of morphine, codeine and 6- mam by mixture of chloroform and isopropanol (9 : 1; v/v). Extracts were analysed by HPLC/MS technique: separation column Waters Spherisorb® 5 μm, ODS2, 4.6 × 100 mm; mobile phase: ammonium acetate : acetonitile (80 : 20; v/v), mobile phase flow rate 0.3 mL/min; mass detection range: 100-400 m/z. Regression and correlation analyses were performed with the probalility level of 0.05. Concentrations of morphine, codeine and 6-mam were determined in saliva samples of the patients with 'opiates' in urine identified by the test strips. Results. Calibration for each analysed substance was done in the concentration range from 0.1 to 1 mg/L and the coefficient of correlation was R2 > 0.99. We obtained following calibration curves: y = 385531x + 14584; y = 398036x + 31542; and y = 524162x - 27105, for morphine, codeine and 6-mam, respectively. Recovery for morphine and codeine determination was 99%, while for 6- mam it was 94%. Limits of detection and quantification of a proposed method were 0.01 mg/L and 0.05 mg/L, respectively. Concentration of morphine in the saliva of the heroin users ranged between 0.54 and 5.82 mg/L, concentration of codeine between 0.05 and 5.33, and 6-mam between 0.01 and 0.68 mg/L. A statistically significant correlation between codeine and 6-mam concentrations was obtained. Conclusion. A proposed HPLC/MS method for morphine, codeine and 6-mam determination in saliva is accurate, simple, cheap and suitable for routine analysis and monitoring of heroin abuse., Uvod/Cilj. Saliva predstavlja alternativni matriks za identifikaciju sredstava zloupotrebe. Cilj ovog rada bio je optimizacija metode pripreme uzorka salive i određivanja metabolita heroina, morfina i 6-monoacetilmorfina (6-mam), i kodeina liquid chromatography-mass spectrometry (LC/MS) metodom i provera metode u realnim uslovima kod heroinomana. Metode. Priprema uzoraka vršena je tečno-tečnom ekstrakcijom uz smešu hloroforma i izopropil alkohola u odnosu 9 : 1. Ekstrakti su analizirani tehnikom HPLC/MS: razdvajanje na koloni Waters Spherisorb® 5 μm, ODS2, 4,6 × 100 mm, vršeno je primenom mobilne faze amonijum-acetat : acetonitril u odnosu 80 : 20 pri protoku od 0,3 mL/min. Masena detekcija je vršena u opsegu masa od 100 do 400 m/z. Primenjene su regresiona i korelaciona analiza za nivo verovatnoće 0,05. Određivanje prisustva morfina, kodeina i 6-mam vršeno je u uzorcima salive kod osoba kod kojih je test trakama utvrđeno prisustvo 'opijata' u urinu. Rezultati. Kalibracija je vršena u opsegu koncentracija 0,1-1 mg/L sa koeficijentom determinacije R2 > 0,99. Dobijene su kalibracione krive: za morfin, y = 385531x + 14584; kodein, y = 398036x + 31542 i 6- monoacetilmorfin, y = 524162x - 27105. Recovery vrednosti za određivanje morfina i kodeina iznosile su 99%, a za 6-mam 94%. Limit detekcije predložene metode iznosio je 0,01 mg/L, a limit kvantifikacije 0,05 mg/L. U salivi uživalaca heroina koncentracija morfina kretala se u opsegu od 0,54 do 5,82 mg/L, kodeina od 0,05 do 5,33, a 6-mam od 0,01 do 0,68 mg/L i dobijena je statistički značajna korelacija između vrednosti za kodein i 6-mam. Zaključak. Predložena HPLC/MS metoda za određivanje sadržaja morfina, kodeina i 6-monoacetilmorfina u salivi je tačna, jednostavna, ekonomična i pogodna za rutinsku primenu, kao i za biomonitoring zloupotrebe heroina.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Determination of morphine, codeine and 6-monoacetylmorphine in saliva of substance-abuse patients using HPLC/MS methods, Određivanje morfina, kodeina i 6-monoacetilmorfina metodom HPLC/MS u salivi heroinskih zavisnika",
volume = "69",
number = "2",
pages = "141-146",
doi = "10.2298/VSP1202141M"
}
Milovanović, V., Ćirić, B., Milenković, J., Kilibarda, V., Ćurčić, M., Vučinić, S.,& Antonijević, B.. (2012). Determination of morphine, codeine and 6-monoacetylmorphine in saliva of substance-abuse patients using HPLC/MS methods. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 69(2), 141-146.
https://doi.org/10.2298/VSP1202141M
Milovanović V, Ćirić B, Milenković J, Kilibarda V, Ćurčić M, Vučinić S, Antonijević B. Determination of morphine, codeine and 6-monoacetylmorphine in saliva of substance-abuse patients using HPLC/MS methods. in Vojnosanitetski pregled. 2012;69(2):141-146.
doi:10.2298/VSP1202141M .
Milovanović, Vesna, Ćirić, Biljana, Milenković, Jasna, Kilibarda, Vesna, Ćurčić, Marijana, Vučinić, Slavica, Antonijević, Biljana, "Determination of morphine, codeine and 6-monoacetylmorphine in saliva of substance-abuse patients using HPLC/MS methods" in Vojnosanitetski pregled, 69, no. 2 (2012):141-146,
https://doi.org/10.2298/VSP1202141M . .
2
2

Toxicokinetics and correlation of carbamazepine salivary and serum concentrations in acute poisonings

Đorđević, Snežana; Kilibarda, Vesna; Vučinić, Slavica; Stojanović, Tomislav; Antonijević, Biljana

(Vojnomedicinska akademija - Institut za naučne informacije, Beograd, 2012)

TY  - JOUR
AU  - Đorđević, Snežana
AU  - Kilibarda, Vesna
AU  - Vučinić, Slavica
AU  - Stojanović, Tomislav
AU  - Antonijević, Biljana
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1828
AB  - Background/Aim. Saliva is a body fluid which, like serum, can be used for determination of concentrations of certain drugs, both in pharmacotherapy as well as in acute poisonings. The aim of this study was to determine carbamazepine concentrations in both saliva and serum in acute poisoning in order to show if there is a correlation between the obtained values, as well as to monitor toxicokinetics of carbamazepine in body fluides. Methods. Saliva and serum samples were obtained from 26 patients treated with carbamazepine and 20 patients acutely poisoned by the drug immediately after their admission in the Emergency Toxicology Unit. Determination of salivary and serum carbamazepine concentrations was performed by the validated high pressure liquid chromatographyultraviolet (HPLC-UV) method. Results. A significant correlation of salivary and serum carbamazepine concentrations in both therapeutic application and acute poisoning (r = 0.9481 and 0.9117, respectively) was confirmed. In acute poisonings the mean ratio between salivary and serum concentrations of carbamazepine (0.43) was similar to the mean ratio after its administration in therapeutic doses (0.39), but there were high inter-individual variations in carbamazepine concentrations in the acutely poisoned patients, as a consequence of different ingested doses of the drug. In acute poisoning the halftime of carbamazepine in saliva and serum was 12.57 h and 6.76 h, respectively. Conclusion. Our results suggest a possible use of saliva as an alternative biological material for determination of carbamazepine concentrations in therapeutic application and acute poisoning as well, and a possible extrapolation of the results obtained in saliva to serum concentrations of carbamazepine.
AB  - Uvod/Cilj. Slično serumu, saliva je biološki materijal koji se može primeniti za određivanje koncentracije lekova kako nakon terapijske primene, tako i u akutnom trovanju. Cilj ovog rada bio je da se odrede koncentracije karbamazepina u salivi i serumu u akutnom trovanju da bi se pokazalo da li postoji korelacija između dobijenih vrednosti, kao i da se isprati toksikokinetika karbamazepina u salivi i serumu. Metode. Uzorci salive i seruma uzeti su od 26 bolesnika na terapiji karbamazepinom i 20 bolesnika akutno otrovanih ovim lekom nakon prijema u toksikološku ambulantu. Određivanje koncentracije karbamazepina vršeno je validovanom metodom visokoefikasne tečne hromatografije sa ultravioletnom detekcijom (HPLC-UV). Rezultati. Potvrđena je značajna korelacija koncentracija karbamazepina u salivi i serumu nakon terapijske primene (r = 0,9481), kao i u akutnom trovanju ovim lekom (r = 0,9117). Prosečni odnos koncentracija karbamazepina u salivi i serumu u akutnim trovanjima (0,43) bio je sličan odgovarajućem parametru nakon terapijske primene leka (0,39), ali je bilo većih interindividualnih razlika u koncentracijama leka u akutnim trovanjima, zbog, najverovatnije, razlika u ingestiranim dozama karbamazepina. U akutnim trovanjima poluvreme eliminacije karbamazepina u serumu bilo je 12,57 h, a u salivi 6,76 h. Zaključak. Dobijeni rezultati govore o mogućoj primeni salive kao biološkog materijala za određivanje koncentracije karbamazepina tokom terapijske primene i u akutnom trovanju, kao i o mogućoj ekstrapolaciji vrednosti koncentracija karbamazepina u salivi na serumske koncentracije ovog leka.
PB  - Vojnomedicinska akademija - Institut za naučne informacije, Beograd
T2  - Vojnosanitetski pregled
T1  - Toxicokinetics and correlation of carbamazepine salivary and serum concentrations in acute poisonings
T1  - Toksikokinetika i korelacija koncentracija karbamazepina u salivi i serumu kod akutnog trovanja
VL  - 69
IS  - 5
SP  - 389
EP  - 393
DO  - 10.2298/VSP1205389D
ER  - 
@article{
author = "Đorđević, Snežana and Kilibarda, Vesna and Vučinić, Slavica and Stojanović, Tomislav and Antonijević, Biljana",
year = "2012",
abstract = "Background/Aim. Saliva is a body fluid which, like serum, can be used for determination of concentrations of certain drugs, both in pharmacotherapy as well as in acute poisonings. The aim of this study was to determine carbamazepine concentrations in both saliva and serum in acute poisoning in order to show if there is a correlation between the obtained values, as well as to monitor toxicokinetics of carbamazepine in body fluides. Methods. Saliva and serum samples were obtained from 26 patients treated with carbamazepine and 20 patients acutely poisoned by the drug immediately after their admission in the Emergency Toxicology Unit. Determination of salivary and serum carbamazepine concentrations was performed by the validated high pressure liquid chromatographyultraviolet (HPLC-UV) method. Results. A significant correlation of salivary and serum carbamazepine concentrations in both therapeutic application and acute poisoning (r = 0.9481 and 0.9117, respectively) was confirmed. In acute poisonings the mean ratio between salivary and serum concentrations of carbamazepine (0.43) was similar to the mean ratio after its administration in therapeutic doses (0.39), but there were high inter-individual variations in carbamazepine concentrations in the acutely poisoned patients, as a consequence of different ingested doses of the drug. In acute poisoning the halftime of carbamazepine in saliva and serum was 12.57 h and 6.76 h, respectively. Conclusion. Our results suggest a possible use of saliva as an alternative biological material for determination of carbamazepine concentrations in therapeutic application and acute poisoning as well, and a possible extrapolation of the results obtained in saliva to serum concentrations of carbamazepine., Uvod/Cilj. Slično serumu, saliva je biološki materijal koji se može primeniti za određivanje koncentracije lekova kako nakon terapijske primene, tako i u akutnom trovanju. Cilj ovog rada bio je da se odrede koncentracije karbamazepina u salivi i serumu u akutnom trovanju da bi se pokazalo da li postoji korelacija između dobijenih vrednosti, kao i da se isprati toksikokinetika karbamazepina u salivi i serumu. Metode. Uzorci salive i seruma uzeti su od 26 bolesnika na terapiji karbamazepinom i 20 bolesnika akutno otrovanih ovim lekom nakon prijema u toksikološku ambulantu. Određivanje koncentracije karbamazepina vršeno je validovanom metodom visokoefikasne tečne hromatografije sa ultravioletnom detekcijom (HPLC-UV). Rezultati. Potvrđena je značajna korelacija koncentracija karbamazepina u salivi i serumu nakon terapijske primene (r = 0,9481), kao i u akutnom trovanju ovim lekom (r = 0,9117). Prosečni odnos koncentracija karbamazepina u salivi i serumu u akutnim trovanjima (0,43) bio je sličan odgovarajućem parametru nakon terapijske primene leka (0,39), ali je bilo većih interindividualnih razlika u koncentracijama leka u akutnim trovanjima, zbog, najverovatnije, razlika u ingestiranim dozama karbamazepina. U akutnim trovanjima poluvreme eliminacije karbamazepina u serumu bilo je 12,57 h, a u salivi 6,76 h. Zaključak. Dobijeni rezultati govore o mogućoj primeni salive kao biološkog materijala za određivanje koncentracije karbamazepina tokom terapijske primene i u akutnom trovanju, kao i o mogućoj ekstrapolaciji vrednosti koncentracija karbamazepina u salivi na serumske koncentracije ovog leka.",
publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd",
journal = "Vojnosanitetski pregled",
title = "Toxicokinetics and correlation of carbamazepine salivary and serum concentrations in acute poisonings, Toksikokinetika i korelacija koncentracija karbamazepina u salivi i serumu kod akutnog trovanja",
volume = "69",
number = "5",
pages = "389-393",
doi = "10.2298/VSP1205389D"
}
Đorđević, S., Kilibarda, V., Vučinić, S., Stojanović, T.,& Antonijević, B.. (2012). Toxicokinetics and correlation of carbamazepine salivary and serum concentrations in acute poisonings. in Vojnosanitetski pregled
Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 69(5), 389-393.
https://doi.org/10.2298/VSP1205389D
Đorđević S, Kilibarda V, Vučinić S, Stojanović T, Antonijević B. Toxicokinetics and correlation of carbamazepine salivary and serum concentrations in acute poisonings. in Vojnosanitetski pregled. 2012;69(5):389-393.
doi:10.2298/VSP1205389D .
Đorđević, Snežana, Kilibarda, Vesna, Vučinić, Slavica, Stojanović, Tomislav, Antonijević, Biljana, "Toxicokinetics and correlation of carbamazepine salivary and serum concentrations in acute poisonings" in Vojnosanitetski pregled, 69, no. 5 (2012):389-393,
https://doi.org/10.2298/VSP1205389D . .
11
7
11

How have the latest trends in toxicology of organophosphates affected our clinical practice?

Vučinić, Slavica; Antonijević, Biljana; Zlatković, M.; Đorđević, D.; Jovanović, M.; Ćurčić, Marijana; Kilibarda, Vesna; Bokonjić, Dubravko

(Elsevier Ireland Ltd, Clare, 2011)

TY  - CONF
AU  - Vučinić, Slavica
AU  - Antonijević, Biljana
AU  - Zlatković, M.
AU  - Đorđević, D.
AU  - Jovanović, M.
AU  - Ćurčić, Marijana
AU  - Kilibarda, Vesna
AU  - Bokonjić, Dubravko
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1469
PB  - Elsevier Ireland Ltd, Clare
C3  - Toxicology Letters
T1  - How have the latest trends in toxicology of organophosphates affected our clinical practice?
VL  - 205
IS  - Supplement
SP  - S56
EP  - S56
DO  - 10.1016/j.toxlet.2011.05.215
ER  - 
@conference{
author = "Vučinić, Slavica and Antonijević, Biljana and Zlatković, M. and Đorđević, D. and Jovanović, M. and Ćurčić, Marijana and Kilibarda, Vesna and Bokonjić, Dubravko",
year = "2011",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Toxicology Letters",
title = "How have the latest trends in toxicology of organophosphates affected our clinical practice?",
volume = "205",
number = "Supplement",
pages = "S56-S56",
doi = "10.1016/j.toxlet.2011.05.215"
}
Vučinić, S., Antonijević, B., Zlatković, M., Đorđević, D., Jovanović, M., Ćurčić, M., Kilibarda, V.,& Bokonjić, D.. (2011). How have the latest trends in toxicology of organophosphates affected our clinical practice?. in Toxicology Letters
Elsevier Ireland Ltd, Clare., 205(Supplement), S56-S56.
https://doi.org/10.1016/j.toxlet.2011.05.215
Vučinić S, Antonijević B, Zlatković M, Đorđević D, Jovanović M, Ćurčić M, Kilibarda V, Bokonjić D. How have the latest trends in toxicology of organophosphates affected our clinical practice?. in Toxicology Letters. 2011;205(Supplement):S56-S56.
doi:10.1016/j.toxlet.2011.05.215 .
Vučinić, Slavica, Antonijević, Biljana, Zlatković, M., Đorđević, D., Jovanović, M., Ćurčić, Marijana, Kilibarda, Vesna, Bokonjić, Dubravko, "How have the latest trends in toxicology of organophosphates affected our clinical practice?" in Toxicology Letters, 205, no. Supplement (2011):S56-S56,
https://doi.org/10.1016/j.toxlet.2011.05.215 . .

Determination of opioides in saliva by HPLC/MS

Cirić, BiIjana; Micović, Marina; Milenković, Jasna; Ćurčić-Jovanović, Marijana; Antonijević, Biljana; Kilibarda, Vesna

(Elsevier Ireland Ltd, Clare, 2008)

TY  - CONF
AU  - Cirić, BiIjana
AU  - Micović, Marina
AU  - Milenković, Jasna
AU  - Ćurčić-Jovanović, Marijana
AU  - Antonijević, Biljana
AU  - Kilibarda, Vesna
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1095
PB  - Elsevier Ireland Ltd, Clare
C3  - Toxicology Letters
T1  - Determination of opioides in saliva by HPLC/MS
VL  - 180
IS  - Supplement
SP  - S158
EP  - S158
DO  - 10.1016/j.toxlet.2008.06.305
ER  - 
@conference{
author = "Cirić, BiIjana and Micović, Marina and Milenković, Jasna and Ćurčić-Jovanović, Marijana and Antonijević, Biljana and Kilibarda, Vesna",
year = "2008",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Toxicology Letters",
title = "Determination of opioides in saliva by HPLC/MS",
volume = "180",
number = "Supplement",
pages = "S158-S158",
doi = "10.1016/j.toxlet.2008.06.305"
}
Cirić, B., Micović, M., Milenković, J., Ćurčić-Jovanović, M., Antonijević, B.,& Kilibarda, V.. (2008). Determination of opioides in saliva by HPLC/MS. in Toxicology Letters
Elsevier Ireland Ltd, Clare., 180(Supplement), S158-S158.
https://doi.org/10.1016/j.toxlet.2008.06.305
Cirić B, Micović M, Milenković J, Ćurčić-Jovanović M, Antonijević B, Kilibarda V. Determination of opioides in saliva by HPLC/MS. in Toxicology Letters. 2008;180(Supplement):S158-S158.
doi:10.1016/j.toxlet.2008.06.305 .
Cirić, BiIjana, Micović, Marina, Milenković, Jasna, Ćurčić-Jovanović, Marijana, Antonijević, Biljana, Kilibarda, Vesna, "Determination of opioides in saliva by HPLC/MS" in Toxicology Letters, 180, no. Supplement (2008):S158-S158,
https://doi.org/10.1016/j.toxlet.2008.06.305 . .

Review of methods for determination of human exposure to organophosphorus pesticides

Simić, A.; Antonijević, Biljana; Kilibarda, Vesna; Vujović, M.; Milosavljević, B.

(Savez farmaceutskih udruženja Srbije, Beograd, 2006)

TY  - CONF
AU  - Simić, A.
AU  - Antonijević, Biljana
AU  - Kilibarda, Vesna
AU  - Vujović, M.
AU  - Milosavljević, B.
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/681
PB  - Savez farmaceutskih udruženja Srbije, Beograd
C3  - Arhiv za farmaciju
T1  - Review of methods for determination of human exposure to organophosphorus pesticides
T1  - Pregled metoda za određivanje izloženosti ljudi organofosfornim pesticidima
VL  - 56
IS  - 4
SP  - 632
EP  - 633
UR  - https://hdl.handle.net/21.15107/rcub_farfar_681
ER  - 
@conference{
author = "Simić, A. and Antonijević, Biljana and Kilibarda, Vesna and Vujović, M. and Milosavljević, B.",
year = "2006",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Review of methods for determination of human exposure to organophosphorus pesticides, Pregled metoda za određivanje izloženosti ljudi organofosfornim pesticidima",
volume = "56",
number = "4",
pages = "632-633",
url = "https://hdl.handle.net/21.15107/rcub_farfar_681"
}
Simić, A., Antonijević, B., Kilibarda, V., Vujović, M.,& Milosavljević, B.. (2006). Review of methods for determination of human exposure to organophosphorus pesticides. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 56(4), 632-633.
https://hdl.handle.net/21.15107/rcub_farfar_681
Simić A, Antonijević B, Kilibarda V, Vujović M, Milosavljević B. Review of methods for determination of human exposure to organophosphorus pesticides. in Arhiv za farmaciju. 2006;56(4):632-633.
https://hdl.handle.net/21.15107/rcub_farfar_681 .
Simić, A., Antonijević, Biljana, Kilibarda, Vesna, Vujović, M., Milosavljević, B., "Review of methods for determination of human exposure to organophosphorus pesticides" in Arhiv za farmaciju, 56, no. 4 (2006):632-633,
https://hdl.handle.net/21.15107/rcub_farfar_681 .

Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos

Antonijević, Biljana; Bokonjić, Dubravko; Stojiljković, Miloš P.; Kilibarda, Vesna; Milovanović, Zoran A.; Nedeljković, M; Maksimović, M

(Wiley, Hoboken, 2005)

TY  - JOUR
AU  - Antonijević, Biljana
AU  - Bokonjić, Dubravko
AU  - Stojiljković, Miloš P.
AU  - Kilibarda, Vesna
AU  - Milovanović, Zoran A.
AU  - Nedeljković, M
AU  - Maksimović, M
PY  - 2005
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/632
AB  - The aim of the study was to examine antidotal potency of trimedoxime in mice poisoned with three direct dimethoxy-substituted organophosphorus inhibitors. In order to assess the protective efficacy of trimedoxime against dichlorvos, heptenophos or monocrotophos, median effective doses and efficacy half-times were calculated. Trimedoxime (24 mg/kg intravenously) was injected 5 min. before 1.3 LD50 intravenously of poisons. Activities of brain, diaphragmal and erythrocyte acetylcholinesterase, as well as of plasma carboxylesterases were determined at different time intervals (10, 40 and 60 min.) after administration of the antidotes. Protective effect of trimedoxime decreased according to the following order: monocrotophos > heptenophos > dichlorvos. Administration of the oxime produced a significant reactivation of central and peripheral acetylcholinesterase inhibited with dichlorvos and heptenophos, with the exception of erythrocyte acetylcholinesterase inhibited by heptenophos. Surprisingly, trimedoxime did not induce reactivation of monocrotophos-inhibited acetylcholinesterase in any of the tissues tested. These organophosphorus compounds produced a significant inhibition of plasma carboxylesterase activity, while administration of trimedoxime led to regeneration of the enzyme activity. The same dose of trimedoxime assured survival of experimental animals poisoned by all three organophosphorus compounds, although the biochemical findings were quite different.
PB  - Wiley, Hoboken
T2  - Basic & Clinical Pharmacology & Toxicology
T1  - Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos
VL  - 96
IS  - 2
SP  - 111
EP  - 117
DO  - 10.1111/j.1742-7843.2005.pto960204.x
ER  - 
@article{
author = "Antonijević, Biljana and Bokonjić, Dubravko and Stojiljković, Miloš P. and Kilibarda, Vesna and Milovanović, Zoran A. and Nedeljković, M and Maksimović, M",
year = "2005",
abstract = "The aim of the study was to examine antidotal potency of trimedoxime in mice poisoned with three direct dimethoxy-substituted organophosphorus inhibitors. In order to assess the protective efficacy of trimedoxime against dichlorvos, heptenophos or monocrotophos, median effective doses and efficacy half-times were calculated. Trimedoxime (24 mg/kg intravenously) was injected 5 min. before 1.3 LD50 intravenously of poisons. Activities of brain, diaphragmal and erythrocyte acetylcholinesterase, as well as of plasma carboxylesterases were determined at different time intervals (10, 40 and 60 min.) after administration of the antidotes. Protective effect of trimedoxime decreased according to the following order: monocrotophos > heptenophos > dichlorvos. Administration of the oxime produced a significant reactivation of central and peripheral acetylcholinesterase inhibited with dichlorvos and heptenophos, with the exception of erythrocyte acetylcholinesterase inhibited by heptenophos. Surprisingly, trimedoxime did not induce reactivation of monocrotophos-inhibited acetylcholinesterase in any of the tissues tested. These organophosphorus compounds produced a significant inhibition of plasma carboxylesterase activity, while administration of trimedoxime led to regeneration of the enzyme activity. The same dose of trimedoxime assured survival of experimental animals poisoned by all three organophosphorus compounds, although the biochemical findings were quite different.",
publisher = "Wiley, Hoboken",
journal = "Basic & Clinical Pharmacology & Toxicology",
title = "Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos",
volume = "96",
number = "2",
pages = "111-117",
doi = "10.1111/j.1742-7843.2005.pto960204.x"
}
Antonijević, B., Bokonjić, D., Stojiljković, M. P., Kilibarda, V., Milovanović, Z. A., Nedeljković, M.,& Maksimović, M.. (2005). Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos. in Basic & Clinical Pharmacology & Toxicology
Wiley, Hoboken., 96(2), 111-117.
https://doi.org/10.1111/j.1742-7843.2005.pto960204.x
Antonijević B, Bokonjić D, Stojiljković MP, Kilibarda V, Milovanović ZA, Nedeljković M, Maksimović M. Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos. in Basic & Clinical Pharmacology & Toxicology. 2005;96(2):111-117.
doi:10.1111/j.1742-7843.2005.pto960204.x .
Antonijević, Biljana, Bokonjić, Dubravko, Stojiljković, Miloš P., Kilibarda, Vesna, Milovanović, Zoran A., Nedeljković, M, Maksimović, M, "Efficacy of trimedoxime in mice poisoned with dichlorvos, heptenophos or monocrotophos" in Basic & Clinical Pharmacology & Toxicology, 96, no. 2 (2005):111-117,
https://doi.org/10.1111/j.1742-7843.2005.pto960204.x . .
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Biopharmaceutical characterization of sustained release matrix tablets based on novel carbomer polymers: formulation and in vivo investigation

Parojčić, Jelena; Đurić, Zorica; Jovanović, M; Ibrić, Svetlana; Kilibarda, Vesna; Jovanović, D; Kovacević, I

(Springer France, Paris, 2005)

TY  - JOUR
AU  - Parojčić, Jelena
AU  - Đurić, Zorica
AU  - Jovanović, M
AU  - Ibrić, Svetlana
AU  - Kilibarda, Vesna
AU  - Jovanović, D
AU  - Kovacević, I
PY  - 2005
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/594
AB  - With the increased interest in modified release dosage forms and drug delivery systems, there is an increasing concern for biopharmaceutical characterization of the formulation in the early stages of drug product development. The main objectives of biopharmaceutical characterization are the in vitro and in vivo evaluation of the selected formulations in order to identify the factors influencing drug release; define the in vitro test methodology that would be predictive of drug products in vivo behavior and develop quantitative in vitro - in vivo correlation. The purpose of this study was to assess the potential of novel carbomer polymers, Carbopol 971P and Carbopol 71G, as a sustained release agents in matrix tablets containing high dosage drug substance. Although chemically identical, the two polymers exhibited substantially different drug release properties in vitro. Hypothetical in vivo drug release profiles were calculated by numerical deconvolution from cumulative urinary excretion data observed in vivo. The obtained results indicated that sound and reliable in vivo drug release profiles could be obtained from urinary excretion data and also, emphasized the need for in vitro testing under a range of experimental conditions in order to develop the biorelevant drug release methodology.
PB  - Springer France, Paris
T2  - European Journal of Drug Metabolism and Pharmacokinetics
T1  - Biopharmaceutical characterization of sustained release matrix tablets based on novel carbomer polymers: formulation and in vivo investigation
VL  - 30
IS  - 1-2
SP  - 99
EP  - 104
DO  - 10.1007/BF03226414
ER  - 
@article{
author = "Parojčić, Jelena and Đurić, Zorica and Jovanović, M and Ibrić, Svetlana and Kilibarda, Vesna and Jovanović, D and Kovacević, I",
year = "2005",
abstract = "With the increased interest in modified release dosage forms and drug delivery systems, there is an increasing concern for biopharmaceutical characterization of the formulation in the early stages of drug product development. The main objectives of biopharmaceutical characterization are the in vitro and in vivo evaluation of the selected formulations in order to identify the factors influencing drug release; define the in vitro test methodology that would be predictive of drug products in vivo behavior and develop quantitative in vitro - in vivo correlation. The purpose of this study was to assess the potential of novel carbomer polymers, Carbopol 971P and Carbopol 71G, as a sustained release agents in matrix tablets containing high dosage drug substance. Although chemically identical, the two polymers exhibited substantially different drug release properties in vitro. Hypothetical in vivo drug release profiles were calculated by numerical deconvolution from cumulative urinary excretion data observed in vivo. The obtained results indicated that sound and reliable in vivo drug release profiles could be obtained from urinary excretion data and also, emphasized the need for in vitro testing under a range of experimental conditions in order to develop the biorelevant drug release methodology.",
publisher = "Springer France, Paris",
journal = "European Journal of Drug Metabolism and Pharmacokinetics",
title = "Biopharmaceutical characterization of sustained release matrix tablets based on novel carbomer polymers: formulation and in vivo investigation",
volume = "30",
number = "1-2",
pages = "99-104",
doi = "10.1007/BF03226414"
}
Parojčić, J., Đurić, Z., Jovanović, M., Ibrić, S., Kilibarda, V., Jovanović, D.,& Kovacević, I.. (2005). Biopharmaceutical characterization of sustained release matrix tablets based on novel carbomer polymers: formulation and in vivo investigation. in European Journal of Drug Metabolism and Pharmacokinetics
Springer France, Paris., 30(1-2), 99-104.
https://doi.org/10.1007/BF03226414
Parojčić J, Đurić Z, Jovanović M, Ibrić S, Kilibarda V, Jovanović D, Kovacević I. Biopharmaceutical characterization of sustained release matrix tablets based on novel carbomer polymers: formulation and in vivo investigation. in European Journal of Drug Metabolism and Pharmacokinetics. 2005;30(1-2):99-104.
doi:10.1007/BF03226414 .
Parojčić, Jelena, Đurić, Zorica, Jovanović, M, Ibrić, Svetlana, Kilibarda, Vesna, Jovanović, D, Kovacević, I, "Biopharmaceutical characterization of sustained release matrix tablets based on novel carbomer polymers: formulation and in vivo investigation" in European Journal of Drug Metabolism and Pharmacokinetics, 30, no. 1-2 (2005):99-104,
https://doi.org/10.1007/BF03226414 . .
3
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Potential beneficial action of adamantanes in mice poisoned with soman

Antonijević, Biljana; Maksimović, Matej; Kilibarda, Vesna; Stojiljković, Miloš P.; Nedeljković, Mirjana; Milovanović, Zoran A.; Bokonjić, Dubravko

(Srpsko lekarsko društvo - Sekcija za toksikologiju, Beograd, 2001)

TY  - JOUR
AU  - Antonijević, Biljana
AU  - Maksimović, Matej
AU  - Kilibarda, Vesna
AU  - Stojiljković, Miloš P.
AU  - Nedeljković, Mirjana
AU  - Milovanović, Zoran A.
AU  - Bokonjić, Dubravko
PY  - 2001
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/305
AB  - The aim of this study was to investigate the efficacy of four pyridinium oximes - pralidoxime (PAM-2), trimedoxime (TMB-4), obidoxime (LuH-6) and HI-6 - alone or in combination with memantine and its principal metabolite 1-amino-3-hydroxymethyl-5-methyl adamantane (Mrz 2/373) against soman in mice. Male Albino mice were pretreated iv with oximes and adamantanes at various times before 1.3 LD-50 of soman iv in order to obtain their ED-50t. In a separate experiment, the brain, dia­phragmai and erythrocytic acetylcholinesterase and plasma carboxylesterase activities were determined after sacrificing mice 5 min after soman 0.75 LD-50. Oxime HI-6 (ED-50 value at 5 min before soman) and adamantanes were administered 5 min before soman. In the combination regimens and in the biochemical experiments the dose of memantine and Mrz 2/373 was fixed at 10 mg/kg iv. Along the tested time intervals, HI-6 afforded the best protection of experimental animals, and calculated EDSOo value of HI-6 was 7.96 µmol/kg. Memantine significantly (up to 9 times) de­creased ED-500 values of all the oximes used, with the exception of TMB-4. Among tested tis­sues, the highest recovery of inhibited acetylcholinesterase was obtained in the diaphragm. Co-administration of adamantanes (memantine, Mrz 2/373) produced a statistically significant in­crease in the erythrocyte acetylcholinesterase activity. It could be concluded that memantine antidotal efficacy could be ascribed to the protection of acetylcholinesterase activity. .
AB  - Pored činjenice daje oksim HI-6 najefikasniji u antagonizovanju toksičnih efekata somana, terapija trovanja ovim nervnim bojnim otrovom još nije u potpunosti zadovoljavajuća. Dosadašnji eksperimenti sa memantinom su pokazali da ovaj derivat adamantana potencira terapijski efekat standardnih antidota pri trovanju organofosfornim jedinjenjima. U ovom radu ispitivana je antidotska efikasnost piridinijumskih oksima - pralidoksima, trimedoksima, obidoksima i HI-6, kao i njihovih kombinacija sa memantinom ili njegovim aktivnim metabolitom Mrz 2/373 u miševa trovanih somanom. Radi dobijanja parametara zaštitne efikasnosti antidota, albino miševima mužjacima su iv aplikovane rastuće doze antidota u određenim vremenskim intervalima ( 1 -60 min) pre 1,3 LD-50 iv somana. Aktivnosti acetilholinesteraze mozga, dijafragme i eritrocita, kao i karboksilesteraza plazme, određivane su nakon iv primene adamantana (10 mg/kg) i/ili oksima HI-6 (3,1 mg/kg; 7,96 µmol/kg) datih 5 min pre 0,75 LD-50 iv somana. Primena oksima HI-6 je obezbedila najbolju zaštitu eksperimentalnih životinja, a srednja efektivna doza u nultom vremenu ED-500 iznosila je 7,96 µmol/kg. Kada je primenjen u kombinaciji sa oksimima, memantin je doveo do značajnog (oko 9 puta) smanjenja HD-500 vrednosti svih oksima, osim trimedoksima. ali je zato poluvreme efikasnosti trimedoksima povećano 4,82 puta. Značajan porast acetilholinesteraze dijafragme dobijen je primenom HI-6, memantina kao i njihove kombinacije. U odnosu na grupu koja je primila samo soman, aktivnost acetilholi­nesteraze eritrocita bila je značajno veća u grupama kojima su davani adamantani i/ili HI-6. Nijedan od primenjenih tretmana nije doveo do statistički značajnog povećanja aktivnosti acetilholinesteraze mozga i karboksilesteraza plazme. Bolji zaštitni efekt kombinacija oksima i memantina u odnosu na same oksime mogao bi se pripisati antikonvulzivnom potencijalu memantina, koji je nekompetitivni antagonista NMDA receptora, ali i izvesnoj zaštiti aktivnog centra acetilholinesteraze dijafragme.
PB  - Srpsko lekarsko društvo - Sekcija za toksikologiju, Beograd
T2  - Archives of Toxicology, Kinetics and Xenobiotic Metabolism
T1  - Potential beneficial action of adamantanes in mice poisoned with soman
T1  - Potencijalna uloga adamantana u trovanju miševa somanom
VL  - 9
IS  - 1-2
SP  - 13
EP  - 20
UR  - https://hdl.handle.net/21.15107/rcub_farfar_305
ER  - 
@article{
author = "Antonijević, Biljana and Maksimović, Matej and Kilibarda, Vesna and Stojiljković, Miloš P. and Nedeljković, Mirjana and Milovanović, Zoran A. and Bokonjić, Dubravko",
year = "2001",
abstract = "The aim of this study was to investigate the efficacy of four pyridinium oximes - pralidoxime (PAM-2), trimedoxime (TMB-4), obidoxime (LuH-6) and HI-6 - alone or in combination with memantine and its principal metabolite 1-amino-3-hydroxymethyl-5-methyl adamantane (Mrz 2/373) against soman in mice. Male Albino mice were pretreated iv with oximes and adamantanes at various times before 1.3 LD-50 of soman iv in order to obtain their ED-50t. In a separate experiment, the brain, dia­phragmai and erythrocytic acetylcholinesterase and plasma carboxylesterase activities were determined after sacrificing mice 5 min after soman 0.75 LD-50. Oxime HI-6 (ED-50 value at 5 min before soman) and adamantanes were administered 5 min before soman. In the combination regimens and in the biochemical experiments the dose of memantine and Mrz 2/373 was fixed at 10 mg/kg iv. Along the tested time intervals, HI-6 afforded the best protection of experimental animals, and calculated EDSOo value of HI-6 was 7.96 µmol/kg. Memantine significantly (up to 9 times) de­creased ED-500 values of all the oximes used, with the exception of TMB-4. Among tested tis­sues, the highest recovery of inhibited acetylcholinesterase was obtained in the diaphragm. Co-administration of adamantanes (memantine, Mrz 2/373) produced a statistically significant in­crease in the erythrocyte acetylcholinesterase activity. It could be concluded that memantine antidotal efficacy could be ascribed to the protection of acetylcholinesterase activity. ., Pored činjenice daje oksim HI-6 najefikasniji u antagonizovanju toksičnih efekata somana, terapija trovanja ovim nervnim bojnim otrovom još nije u potpunosti zadovoljavajuća. Dosadašnji eksperimenti sa memantinom su pokazali da ovaj derivat adamantana potencira terapijski efekat standardnih antidota pri trovanju organofosfornim jedinjenjima. U ovom radu ispitivana je antidotska efikasnost piridinijumskih oksima - pralidoksima, trimedoksima, obidoksima i HI-6, kao i njihovih kombinacija sa memantinom ili njegovim aktivnim metabolitom Mrz 2/373 u miševa trovanih somanom. Radi dobijanja parametara zaštitne efikasnosti antidota, albino miševima mužjacima su iv aplikovane rastuće doze antidota u određenim vremenskim intervalima ( 1 -60 min) pre 1,3 LD-50 iv somana. Aktivnosti acetilholinesteraze mozga, dijafragme i eritrocita, kao i karboksilesteraza plazme, određivane su nakon iv primene adamantana (10 mg/kg) i/ili oksima HI-6 (3,1 mg/kg; 7,96 µmol/kg) datih 5 min pre 0,75 LD-50 iv somana. Primena oksima HI-6 je obezbedila najbolju zaštitu eksperimentalnih životinja, a srednja efektivna doza u nultom vremenu ED-500 iznosila je 7,96 µmol/kg. Kada je primenjen u kombinaciji sa oksimima, memantin je doveo do značajnog (oko 9 puta) smanjenja HD-500 vrednosti svih oksima, osim trimedoksima. ali je zato poluvreme efikasnosti trimedoksima povećano 4,82 puta. Značajan porast acetilholinesteraze dijafragme dobijen je primenom HI-6, memantina kao i njihove kombinacije. U odnosu na grupu koja je primila samo soman, aktivnost acetilholi­nesteraze eritrocita bila je značajno veća u grupama kojima su davani adamantani i/ili HI-6. Nijedan od primenjenih tretmana nije doveo do statistički značajnog povećanja aktivnosti acetilholinesteraze mozga i karboksilesteraza plazme. Bolji zaštitni efekt kombinacija oksima i memantina u odnosu na same oksime mogao bi se pripisati antikonvulzivnom potencijalu memantina, koji je nekompetitivni antagonista NMDA receptora, ali i izvesnoj zaštiti aktivnog centra acetilholinesteraze dijafragme.",
publisher = "Srpsko lekarsko društvo - Sekcija za toksikologiju, Beograd",
journal = "Archives of Toxicology, Kinetics and Xenobiotic Metabolism",
title = "Potential beneficial action of adamantanes in mice poisoned with soman, Potencijalna uloga adamantana u trovanju miševa somanom",
volume = "9",
number = "1-2",
pages = "13-20",
url = "https://hdl.handle.net/21.15107/rcub_farfar_305"
}
Antonijević, B., Maksimović, M., Kilibarda, V., Stojiljković, M. P., Nedeljković, M., Milovanović, Z. A.,& Bokonjić, D.. (2001). Potential beneficial action of adamantanes in mice poisoned with soman. in Archives of Toxicology, Kinetics and Xenobiotic Metabolism
Srpsko lekarsko društvo - Sekcija za toksikologiju, Beograd., 9(1-2), 13-20.
https://hdl.handle.net/21.15107/rcub_farfar_305
Antonijević B, Maksimović M, Kilibarda V, Stojiljković MP, Nedeljković M, Milovanović ZA, Bokonjić D. Potential beneficial action of adamantanes in mice poisoned with soman. in Archives of Toxicology, Kinetics and Xenobiotic Metabolism. 2001;9(1-2):13-20.
https://hdl.handle.net/21.15107/rcub_farfar_305 .
Antonijević, Biljana, Maksimović, Matej, Kilibarda, Vesna, Stojiljković, Miloš P., Nedeljković, Mirjana, Milovanović, Zoran A., Bokonjić, Dubravko, "Potential beneficial action of adamantanes in mice poisoned with soman" in Archives of Toxicology, Kinetics and Xenobiotic Metabolism, 9, no. 1-2 (2001):13-20,
https://hdl.handle.net/21.15107/rcub_farfar_305 .

Anti-inflammatory and anti-ulcer activity of Achillea alexandri-regis

Kundaković, Tatjana; Dobrić, Silva; Bokonjić, Dubravko; Dragojević-Simić, Viktorija; Kilibarda, Vesna; Kovacević, N

(Govi-Verlag Gmbh, Eschborn, 2000)

TY  - JOUR
AU  - Kundaković, Tatjana
AU  - Dobrić, Silva
AU  - Bokonjić, Dubravko
AU  - Dragojević-Simić, Viktorija
AU  - Kilibarda, Vesna
AU  - Kovacević, N
PY  - 2000
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/238
PB  - Govi-Verlag Gmbh, Eschborn
T2  - Pharmazie
T1  - Anti-inflammatory and anti-ulcer activity of Achillea alexandri-regis
VL  - 55
IS  - 11
SP  - 866
EP  - 867
UR  - https://hdl.handle.net/21.15107/rcub_farfar_238
ER  - 
@article{
author = "Kundaković, Tatjana and Dobrić, Silva and Bokonjić, Dubravko and Dragojević-Simić, Viktorija and Kilibarda, Vesna and Kovacević, N",
year = "2000",
publisher = "Govi-Verlag Gmbh, Eschborn",
journal = "Pharmazie",
title = "Anti-inflammatory and anti-ulcer activity of Achillea alexandri-regis",
volume = "55",
number = "11",
pages = "866-867",
url = "https://hdl.handle.net/21.15107/rcub_farfar_238"
}
Kundaković, T., Dobrić, S., Bokonjić, D., Dragojević-Simić, V., Kilibarda, V.,& Kovacević, N.. (2000). Anti-inflammatory and anti-ulcer activity of Achillea alexandri-regis. in Pharmazie
Govi-Verlag Gmbh, Eschborn., 55(11), 866-867.
https://hdl.handle.net/21.15107/rcub_farfar_238
Kundaković T, Dobrić S, Bokonjić D, Dragojević-Simić V, Kilibarda V, Kovacević N. Anti-inflammatory and anti-ulcer activity of Achillea alexandri-regis. in Pharmazie. 2000;55(11):866-867.
https://hdl.handle.net/21.15107/rcub_farfar_238 .
Kundaković, Tatjana, Dobrić, Silva, Bokonjić, Dubravko, Dragojević-Simić, Viktorija, Kilibarda, Vesna, Kovacević, N, "Anti-inflammatory and anti-ulcer activity of Achillea alexandri-regis" in Pharmazie, 55, no. 11 (2000):866-867,
https://hdl.handle.net/21.15107/rcub_farfar_238 .
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