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Variability in Zidovudine Serum Concentrations
Author(s) -
Fletcher Courtney V.,
Balfour Henry H.
Publication year - 1996
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1996.tb03044.x
Subject(s) - zidovudine , pharmacokinetics , regimen , dosing , medicine , standard deviation , human immunodeficiency virus (hiv) , serum concentration , pharmacology , statistics , mathematics , viral disease , immunology
This study explored the variability of zidovudine concentrations with computer simulations and measured concentrations. A one‐compartment oral absorption model was selected to characterize zidovudine disposition. Mean (± standard deviation) values for the pharmacokinetic parameters were taken from the literature. Five different Monte Carlo simulations (50 each) were performed of zidovudine concentrations following repetitive administration of 100‐mg oral doses 6 times/day in patients weighing 45–85 kg. A sixth simulation considered a weight‐adjusted regimen. Predicted concentrations were compared with those measured in 30 HIV‐infected persons receiving 100 mg/dose. Predicted concentrations 1 hour after 100 mg was administered fell in the range of 0.52–5.18 μM; measured values in 30 patients were 0.54–3.07 μM. This study confirms substantial variability in zidovudine serum concentrations. The simulation study of a weight‐adjusted regimen suggests one possibility to reduce this variability. These observations provide a basis to explore dosing strategies that control for pharmacokinetic and perhaps pharmacodynamic sources of interpatient variability.