Population pharmacokinetics of zidovudine. The Veterans Administration Cooperative Studies Group

Abstract

The epidemic of human immunodeficiency virus infection has forced an unprecedented acceleration of drug development. The lack of effective therapy at present against many of the infectious complications of acquired immunodeficiency syndrome (AIDS) has forced the rapid clinical introduction of new agents. Population pharmacokinetic models are particularly attractive as a means of assessing drug disposition in cohorts different from those studied during necessarily abbreviated phase I trials. We have used the population pharmacokinetics model as implemented by the computer program NONMEM to study the distribution of zidovudine in a large number of patients who have AIDS-related complex and who are therefore at an earlier stage of immunosuppression than subjects in other studies. We confirm a clearance of drug identical to that seen by traditional methods but a larger volume of distribution than estimated previously in patients with AIDS. Possible reasons for this discrepancy and the use of this method in the development of antiretroviral therapy are discussed.