VARIABILITY IN ZIDOVUDINE SERUM CONCENTRATIONS

This study explored the variability of zidovudine concentrations with computer simulations and measured concentrations. A one-compartment or al absorption model was selected to characterize zidovudine dispositio n. Mean (I Standard deviation) values for the pharmacokinetic paramete rs were taken from the literature. Five different Monte Carlo simulati ons (SO each) were performed of zidovudine concentrations following re petitive administration of 100-mg oral doses 6 times/day in patients w eighing 45-85 kg. A sixth simulation considered a weight-adjusted regi men. 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 mu M; measured values in 30 patients were 0.54-3.07 mu M. This study conf irms substantial variability in zidovudine serum concentrations. The s imulation study of a weight-adjusted regimen suggests one possibility to reduce this variability. These observations provide a basis to expl ore dosing strategies that control for pharmacokinetic and perhaps pha rmacodynamic sources of interpatient variability.