       Document 0641
 DOCN  M95A0641
 TI    Exposure to zidovudine in the fetal baboon. American Pediatric Society
       104th annual meeting and Society for Pediatric Research 63rd annual
       meeting; 1994 May 2-5; Seattle.
 DT    9510
 AU    Garland M; Stark RI; Szeto HH; Myers MM; Dept of Peds, College P & S
       Columbia Univ., NY, NY, USA.
 SO    Pediatr AIDS HIV Infect. 1994 Oct;5(5):315 (unnumbered abstract). Unique
       Identifier : AIDSLINE AIDS/95330403
 AB    Zidovudine (ZDV) is currently administered to HIV-infected women during
       pregnancy. The drug is also being studied as an agent for prevention of
       vertical transmission of HIV and for treatment of infected fetuses.
       Better understanding of the pharmacokinetics of ZDV in the
       maternal-fetal unit will improve prediction of effects on the fetus and
       provide a rational basis for fetal therapy. This study evaluates the
       degree of fetal drug exposure in chronically catheterized pregnant
       baboons. Intravenous administration of ZDV to steady state over a range
       of infusion rates (7-40 mg/h) was studied from 112-167 days gestation
       (term = 175 days). Both ZDV and zidovudine-glucuronide (ZDV-g) were
       measured by RIA. First order kinetics were demonstrated at all rates of
       infusion. Steady state values of maternal ZDV were 213 to 996 ng/ml
       which encompass the therapeutic range. Fetal levels were 0.75 +/- .07 of
       maternal values. Means (+/- SD) of half-life (T1/2, min), clearance (CL,
       l/h), and volume of distribution (VD, l) are shown below. TABULAR DATA,
       SEE PUBLISHED ABSTRACT. Surprisingly, there were no differences in any
       measure between pregnant and nonpregnant animals. The fetal T1/2 of ZDV
       was not significantly different from that of the mother. Fetal T1/2 of
       ZDV-g was more than twice that of the mother but was highly variable (p
       < .06). Since glucuronides are not thought to cross the placenta, the
       presence of ZDV-g in the fetus suggests fetal metabolism of the drug.
       The T1/2s of ZDV and ZDV-g in amniotic fluid were much longer than those
       in either the mother or fetus. The mechanisms regulating drug
       disposition and metabolism in amniotic fluid are undefined. Further
       studies with chronic dosing will be conducted to understand the impact
       of amniotic fluid as a reservoir of drug for the fetus and the dynamics
       of fetal hepatic glucuronidation.
 DE    Animal  Female  Fetus/*METABOLISM  Half-Life  Infusions, Intravenous
       Papio  Pregnancy  Radioimmunoassay  Support, U.S. Gov't, P.H.S.
       Zidovudine/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS  MEETING ABSTRACT
       JOURNAL ARTICLE

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

