STRATEGIES FOR CONTROL OF ZIDOVUDINE CONCENTRATIONS IN SERUM

There are several clinical scenarios in which knowledge of zidovudine disposition may be important, This study evaluated the clinical utilit y of pharmacokinetic parameters for zidovudine derived from sparse ser um concentration data obtained in an outpatient setting, Twelve human immunodeficiency virus-infected participants had two serum zidovudine concentration determinations obtained on two different clinic visits, 2 to 38 days apart, Zidovudine concentrations were measured by radioim munoassay, A one compartment oral absorption model was used to describ e zidovudine disposition, Three different approaches were used to esti mate pharmacokinetic parameters: Bayesian estimation with one or two c oncentrations and least squares with one concentration, The ability of these parameters to predict concentrations measured during the second clinic visit was assessed by calculation of precision and bias and co mpared with predictions using standard fixed or weight-adjusted parame ters, Estimated pharmacokinetic parameters for zidovudine were consist ent with literature values; there was no statistically significant dif ference among the parameters calculated with the three estimation stra tegies, Absorptive phase concentrations were poorly predicted by all m ethods (mean percent bias, 157 to 249%; mean percent precision, 389 to 537%), Predictive ability for concentrations obtained in the eliminat ion phase,vas strikingly improved: mean percent bias, -17 to 70%; mean percent precision, 40 to 95%, Bayesian and least-squares estimated pa rameters were statistically better than fixed-parameter values for pre dicting concentrations in the elimination phase, These observations pr ovide a modeling framework to determine pharmacokinetic disposition of zidovudine in an individual, screen for the existence of a drug inter action, and conduct concentration-controlled clinical trials.