Zidovudine kinetics in the pregnant baboon.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Zidovudine kinetics in the pregnant baboon.

J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Feb 1;11(2):117-27. Unique Identifier : AIDSLINE MED/96147311
Garland M; Szeto HH; Daniel SS; Tropper PJ; Myers MM; Stark RI; College of Physicians and Surgeons, Columbia University, New; York, NY 10032, USA.

Abstract: 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 the maternal pharmacokinetics from a series of experiments to delineate more clearly the complex maternal-fetal pharmacokinetics and the effects of AZT in the chronically instrumented maternal and fetal baboon during both steady state intravenous infusion and oral bolus dosage regimens. Two results of major clinical importance were found. First, during pregnancy, both the clearance and volume of distribution of AZT were increased. Plasma clearance in the pregnant animals was 51 +/- 10 ml/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 with 2.2 +/- 0.61/kg. Second, with continuous intravenous infusion plasma drug concentrations were easily maintained in the therapeutic range, whereas with oral administration plasma concentration fell below therapeutic levels within 2 h of the dose being given. Because maternal plasma concentrations are a major determinant of drug concentration achieved 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 prevention of HIV infection in children.

Keywords: Absorption Administration, Oral Animal Animals, Newborn/METABOLISM Antiviral Agents/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS Biological Availability Female Fetal Blood Gestational Age Half-Life Infusions, Intravenous Maternal-Fetal Exchange Papio Pregnancy Pregnancy, Animal/*METABOLISM Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Tissue Distribution Zidovudine/*ANALOGS & DERIVATIVES/ADMINISTRATION & DOSAGE/ *PHARMACOKINETICS JOURNAL ARTICLE
960530
M9651038

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