Abstract
This study explored the variability of zidovudine concentrations with computer simulations anti 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.
Original language | English (US) |
---|---|
Pages (from-to) | 1154-1158 |
Number of pages | 5 |
Journal | Pharmacotherapy |
Volume | 16 |
Issue number | 6 I |
DOIs | |
State | Published - 1996 |
Externally published | Yes |
ASJC Scopus subject areas
- Pharmacology (medical)