ZIDOVUDINE KINETICS IN THE PREGNANT BABOON

The devastating impact of human immunodeficiency virus (HIV) infection during pregnancy has made the pharmacologic evaluation of potentially therapeutic agents of high priority. The results presented here are t he maternal pharmacokinetics from a series of experiments to delineate more clearly the complex maternal-fetal pharmacokinetics and the effe cts of AZT in the chronically instrumented maternal and fetal baboon d uring both steady state intravenous infusion and oral bolus dosage reg imens. Two results of major clinical importance were found. First, dur ing pregnancy, both the clearance and volume of distribution of AZT we re increased. Plasma clearance in the pregnant animals was 51 +/- 10 m l/min/kg compared with 37 +/- 2 ml/min/kg in the nonpregnant animals, and steady state volume of distribution was 3.7 +/- 1.21/kg compared w ith 2.2 +/- 0.61/kg. Second, with continuous intravenous infusion plas ma drug concentrations were easily maintained in the therapeutic range , whereas with oral administration plasma concentration fell below the rapeutic levels within 2 h of the dose being given. Because maternal p lasma concentrations are a major determinant of drug concentration ach ieved in the fetus, an understanding of drug kinetics in pregnancy is of vital importance when making recommendations regarding optimal drug therapy during pregnancy to maximize the beneficial effect-the preven tion of HIV infection in children.