Document 0493
 DOCN  M9650493
 TI    Zidovudine kinetics in the pregnant baboon.
 DT    9605
 AU    Garland M; Szeto HH; Daniel SS; Tropper PJ; Myers MM; Stark RI; College
       of Physicians and Surgeons, Columbia University, New; York, NY 10032,
       USA.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Feb 1;11(2):117-27.
       Unique Identifier : AIDSLINE MED/96147311
 AB    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.
 DE    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

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).