TY  - JOUR
AU  - Bajraktarević, Azra
AU  - Mehmedagić, Aida
AU  - Vučićević, Katarina
AU  - Kulić, Mehmed
AU  - Miljković, Branislava
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2667
AB  - Being a narrow therapeutic index drug, digoxin may cause harm if dosed without regular measurements of serum levels. Due to various limitations in its dosing, different challenges still exist in clinical practice. This study aimed to assess digoxin though concentrations after different regimens in adult and elderly patients, and to identify predictor variables for the ratio of given dose and digoxin trough level. This was prospective open-label study. Digoxin was administered per os as 0.125. or 0.25 mg during different continuous and interrupted dosage regimens. Study protocol allowed an additional therapy according to contemporary guidelines. Digoxin concentrations were determined using Abbott AxSYM Digoxin II assay in trough samples (1-3 per patient) after 3-4 weeks stable regimen. In total, 191 concentrations (104 patients) were analyzed. Digoxin weekly dose was in range 0.375-1.75 mg. On average, we observed slightly lower digoxin levels in 1-117 patients. Results showed that in patients receiving digoxin with interrupted dosage regimen post pause digoxin level was statistically significantly lower than pre-pause (p  lt  0.05). Based on multiple linear regression, the ratio of given dose and trough concentration was mainly predicted by clearance creatinine, and to lesser extent by patient's ideal body weight. Interrupted dosing schedule shows greater variability in drug levels comparing to continuous dosing, and it additionally causes difficulties in reaching and maintaining steady trough levels between doses. Hence, individualization of dosing regimen should he carefully guided based on target levels and not solely on clinical signs and symptoms.
PB  - Polskie Towarzystwo Farmaceutyczne, Warsaw
T2  - Acta Poloniae Pharmaceutica - Drug Research
T1  - The posology and trough concentrations of digoxin in adult and elderly patients
VL  - 73
IS  - 5
SP  - 1361
EP  - 1368
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2667
ER  - 

@article{
author = "Bajraktarević, Azra and Mehmedagić, Aida and Vučićević, Katarina and Kulić, Mehmed and Miljković, Branislava",
year = "2016",
abstract = "Being a narrow therapeutic index drug, digoxin may cause harm if dosed without regular measurements of serum levels. Due to various limitations in its dosing, different challenges still exist in clinical practice. This study aimed to assess digoxin though concentrations after different regimens in adult and elderly patients, and to identify predictor variables for the ratio of given dose and digoxin trough level. This was prospective open-label study. Digoxin was administered per os as 0.125. or 0.25 mg during different continuous and interrupted dosage regimens. Study protocol allowed an additional therapy according to contemporary guidelines. Digoxin concentrations were determined using Abbott AxSYM Digoxin II assay in trough samples (1-3 per patient) after 3-4 weeks stable regimen. In total, 191 concentrations (104 patients) were analyzed. Digoxin weekly dose was in range 0.375-1.75 mg. On average, we observed slightly lower digoxin levels in 1-117 patients. Results showed that in patients receiving digoxin with interrupted dosage regimen post pause digoxin level was statistically significantly lower than pre-pause (p  lt  0.05). Based on multiple linear regression, the ratio of given dose and trough concentration was mainly predicted by clearance creatinine, and to lesser extent by patient's ideal body weight. Interrupted dosing schedule shows greater variability in drug levels comparing to continuous dosing, and it additionally causes difficulties in reaching and maintaining steady trough levels between doses. Hence, individualization of dosing regimen should he carefully guided based on target levels and not solely on clinical signs and symptoms.",
publisher = "Polskie Towarzystwo Farmaceutyczne, Warsaw",
journal = "Acta Poloniae Pharmaceutica - Drug Research",
title = "The posology and trough concentrations of digoxin in adult and elderly patients",
volume = "73",
number = "5",
pages = "1361-1368",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2667"
}

Bajraktarević, A., Mehmedagić, A., Vučićević, K., Kulić, M.,& Miljković, B.. (2016). The posology and trough concentrations of digoxin in adult and elderly patients. in Acta Poloniae Pharmaceutica - Drug Research
Polskie Towarzystwo Farmaceutyczne, Warsaw., 73(5), 1361-1368.
https://hdl.handle.net/21.15107/rcub_farfar_2667

Bajraktarević A, Mehmedagić A, Vučićević K, Kulić M, Miljković B. The posology and trough concentrations of digoxin in adult and elderly patients. in Acta Poloniae Pharmaceutica - Drug Research. 2016;73(5):1361-1368.
https://hdl.handle.net/21.15107/rcub_farfar_2667 .

Bajraktarević, Azra, Mehmedagić, Aida, Vučićević, Katarina, Kulić, Mehmed, Miljković, Branislava, "The posology and trough concentrations of digoxin in adult and elderly patients" in Acta Poloniae Pharmaceutica - Drug Research, 73, no. 5 (2016):1361-1368,
https://hdl.handle.net/21.15107/rcub_farfar_2667 .

TY  - JOUR
AU  - Kovačević, Ivan
AU  - Miljković, Branislava
AU  - Brzaković, Branka
AU  - Mehmedagić, Aida
AU  - Brujić, Jelena
AU  - Milanović, Marija
AU  - Pokrajac, Milena
PY  - 2004
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/497
AB  - The aim of this study was to evaluate the influence of smoking on the urine paracetamol elimination. Fourteen healthy female volunteers took part in this controlled study. Seven (23+/-3 years; 50 +/- 2 kg; x+/-SD) were non-smokers and seven (26 +/- 9 years; 58 +/- 8 kg) were smokers (15 cigarettes per day). After administration of 500 mg of paracetamol, urine sampling was performed at specific times (before drug administration and 1, 2, 3, 4, 6, 9, 12, 16 and 24 hours after). The bioanalytical method used for determination of hydrolyzed paracetamol conjugates in urine samples was UV-spectrometry. The obtained pharmacokinetic parameters of paracetamol, first-order elimination rate constant (â) and elimination half-life (t1/2â), were statistically compared between non-smokers and smokers. There were no significant differences in both elimination parameters (â 0.311 1/h; t1/2â 2.23 h non-smokers vs. â 0.346 1/h; t1/2â 2.19 h smokers) between the groups. However, the differences obtained in inter-individual variability in pharmacokinetic parameters (â SD 0.013 , KV 13.4 % ; t1/2â SD 0.227, KV 4.57% nonsmokers vs. â SD 0.108 , KV 90 % ; t1/2â SD 0.684 , KV 14 % smokers) indicate relatively low predictability of paracetamol elimination in smokers. That requires higher attention in dosing this drug in smokers, especially if some other factors also influence.
AB  - U radu je ispitivan uticaj sastojaka duvanskog dima na brzinu eliminacije paracetamola urinom. U kontrolisanom ispitivanju je učestvovalo 14 zdravih dobrovoljaca ženskog pola. Sedam su bili nepušači (23±8 godine; 50±2 kg: X±SD), a sedam (26±9 godina; 58±8 kg; X±SD) pušači (15 cigareta dnevno). Određivan je „ukupan” paracetamol u urinu UV- spektrometrijskom metodom, posle hidrolize konjugata paracetamola i oksidacije dobijenog proizvoda, u prisustvu hipobromita, do obojenog jedinjenja - derivata indofenola. Farmakokinetičkom analizom izmerenih koncentracija u urinu izračunati su farmakokinetički parametri: konstanta brzine eliminacije (â) i poluvreme eliminacije paracetamola (t1/2â). Mada vrednosti ovih parametara kod pušača ukazuju na bržu eliminaciju paracetamola, statističkim poređenjem farmakokinetičkih parametara eliminacije kod pušača (â=0,346 1/h i t1/2â=2,19 h) i nepušača (â=0,311 1/h, t1/2â=2,23 h), nije dobijena značajna razlika ( P lt 0,05). Veće vrednosti SD=0,108 i KV=90 % za â i SD=0,684 i KV= 14, 25 % za t1/2â u grupi pušača, u poređenju sa istim parametrima u grupi nepušača (SD=0,013 i KV=13,4 % za â i SD=0,227 i KV=4,57 % za t1/2â), pokazuju veću inter-individualnu varijabilnost farmakokinetičkih parametara eliminacije paracetamola kod pušača. Posledica je relativno niska predvidivost farmakokinetike paracetamola kod pušača, pa je kod njih potrebna veća pažnja u doziranju leka, naročito ako postoji i uticaj drugih faktora farmakokinetičke varijabilnosti.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - The influence of smoking on the urine paracetamol elimination
T1  - Eliminacija paracetamola urinom kod pušača
VL  - 54
IS  - 5
SP  - 655
EP  - 664
UR  - https://hdl.handle.net/21.15107/rcub_farfar_497
ER  - 

@article{
author = "Kovačević, Ivan and Miljković, Branislava and Brzaković, Branka and Mehmedagić, Aida and Brujić, Jelena and Milanović, Marija and Pokrajac, Milena",
year = "2004",
abstract = "The aim of this study was to evaluate the influence of smoking on the urine paracetamol elimination. Fourteen healthy female volunteers took part in this controlled study. Seven (23+/-3 years; 50 +/- 2 kg; x+/-SD) were non-smokers and seven (26 +/- 9 years; 58 +/- 8 kg) were smokers (15 cigarettes per day). After administration of 500 mg of paracetamol, urine sampling was performed at specific times (before drug administration and 1, 2, 3, 4, 6, 9, 12, 16 and 24 hours after). The bioanalytical method used for determination of hydrolyzed paracetamol conjugates in urine samples was UV-spectrometry. The obtained pharmacokinetic parameters of paracetamol, first-order elimination rate constant (â) and elimination half-life (t1/2â), were statistically compared between non-smokers and smokers. There were no significant differences in both elimination parameters (â 0.311 1/h; t1/2â 2.23 h non-smokers vs. â 0.346 1/h; t1/2â 2.19 h smokers) between the groups. However, the differences obtained in inter-individual variability in pharmacokinetic parameters (â SD 0.013 , KV 13.4 % ; t1/2â SD 0.227, KV 4.57% nonsmokers vs. â SD 0.108 , KV 90 % ; t1/2â SD 0.684 , KV 14 % smokers) indicate relatively low predictability of paracetamol elimination in smokers. That requires higher attention in dosing this drug in smokers, especially if some other factors also influence., U radu je ispitivan uticaj sastojaka duvanskog dima na brzinu eliminacije paracetamola urinom. U kontrolisanom ispitivanju je učestvovalo 14 zdravih dobrovoljaca ženskog pola. Sedam su bili nepušači (23±8 godine; 50±2 kg: X±SD), a sedam (26±9 godina; 58±8 kg; X±SD) pušači (15 cigareta dnevno). Određivan je „ukupan” paracetamol u urinu UV- spektrometrijskom metodom, posle hidrolize konjugata paracetamola i oksidacije dobijenog proizvoda, u prisustvu hipobromita, do obojenog jedinjenja - derivata indofenola. Farmakokinetičkom analizom izmerenih koncentracija u urinu izračunati su farmakokinetički parametri: konstanta brzine eliminacije (â) i poluvreme eliminacije paracetamola (t1/2â). Mada vrednosti ovih parametara kod pušača ukazuju na bržu eliminaciju paracetamola, statističkim poređenjem farmakokinetičkih parametara eliminacije kod pušača (â=0,346 1/h i t1/2â=2,19 h) i nepušača (â=0,311 1/h, t1/2â=2,23 h), nije dobijena značajna razlika ( P lt 0,05). Veće vrednosti SD=0,108 i KV=90 % za â i SD=0,684 i KV= 14, 25 % za t1/2â u grupi pušača, u poređenju sa istim parametrima u grupi nepušača (SD=0,013 i KV=13,4 % za â i SD=0,227 i KV=4,57 % za t1/2â), pokazuju veću inter-individualnu varijabilnost farmakokinetičkih parametara eliminacije paracetamola kod pušača. Posledica je relativno niska predvidivost farmakokinetike paracetamola kod pušača, pa je kod njih potrebna veća pažnja u doziranju leka, naročito ako postoji i uticaj drugih faktora farmakokinetičke varijabilnosti.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "The influence of smoking on the urine paracetamol elimination, Eliminacija paracetamola urinom kod pušača",
volume = "54",
number = "5",
pages = "655-664",
url = "https://hdl.handle.net/21.15107/rcub_farfar_497"
}

Kovačević, I., Miljković, B., Brzaković, B., Mehmedagić, A., Brujić, J., Milanović, M.,& Pokrajac, M.. (2004). The influence of smoking on the urine paracetamol elimination. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 54(5), 655-664.
https://hdl.handle.net/21.15107/rcub_farfar_497

Kovačević I, Miljković B, Brzaković B, Mehmedagić A, Brujić J, Milanović M, Pokrajac M. The influence of smoking on the urine paracetamol elimination. in Arhiv za farmaciju. 2004;54(5):655-664.
https://hdl.handle.net/21.15107/rcub_farfar_497 .

Kovačević, Ivan, Miljković, Branislava, Brzaković, Branka, Mehmedagić, Aida, Brujić, Jelena, Milanović, Marija, Pokrajac, Milena, "The influence of smoking on the urine paracetamol elimination" in Arhiv za farmaciju, 54, no. 5 (2004):655-664,
https://hdl.handle.net/21.15107/rcub_farfar_497 .