       Document 1006
 DOCN  M9541006
 TI    Transfer of dideoxyinosine across the human isolated placenta.
 DT    9504
 AU    Henderson GI; Perez AB; Yang Y; Hamby RL; Schenken RS; Schenker S;
       Department of Medicine, University of Texas Health Science Center; at
       San Antonio 78284-7878.
 SO    Br J Clin Pharmacol. 1994 Sep;38(3):237-42. Unique Identifier : AIDSLINE
       MED/95127427
 AB    1. Dideoxyinosine (ddI) has recently been approved for the treatment of
       patients with HIV infection. As increasing numbers of such patients are
       pregnant, we wished to define the rate and mechanism(s) of ddI transfer
       by the placenta to the foetus. Using isolated single perfused human term
       placental cotyledons, the drug was shown to cross the placenta from
       mother to foetus at a rate of 25% that of a freely diffusible marker,
       antipyrine, and at about half the rate of zidovudine (AZT). The transfer
       of ddI was similar in both directions (maternal to foetal and the
       reverse), equal to that of L-glucose, a passively transported sugar, and
       was not inhibited by excess inosine or uric acid (structural analogues
       of ddI). ddI did not cross to the foetus against a concentration
       gradient. The transport process appeared to be passive and it was not
       altered by AZT. 2. ddI was not metabolized in the Krebs Ringer
       buffer/albumin perfusate, and placental homogenates converted only 4% of
       ddI to hypoxanthine over the 4 h incubation. However, when maternal term
       or cord blood was incubated with ddI for 3 h, 50% of the drug was
       converted to hypoxanthine in maternal blood and to hypoxanthine and uric
       acid in cord blood. 3. Thus, ddI metabolism in maternal blood should
       decrease its net transfer to the foetus in vivo. In the foetal
       circulation, ddI will be further metabolized by erythrocytes to
       hypoxanthine and possibly to uric acid. Hence, the fraction of
       administered ddI delivered to foetal tissues should be much lower than
       that of AZT.
 DE    Antipyrine/METABOLISM/PHARMACOKINETICS  Biological Transport
       Chromatography, High Pressure Liquid  Comparative Study
       Didanosine/*METABOLISM/PHARMACOKINETICS  Female
       Glucose/METABOLISM/PHARMACOKINETICS  Human  Hydrogen-Ion Concentration
       Hypoxanthines/METABOLISM  In Vitro  Inosine/PHARMACOLOGY
       *Maternal-Fetal Exchange/DRUG EFFECTS/PHYSIOLOGY  Perfusion
       Placenta/*METABOLISM  Pregnancy  Support, U.S. Gov't, P.H.S.  Uric
       Acid/PHARMACOLOGY  Zidovudine/METABOLISM/PHARMACOLOGY/PHARMACOKINETICS
       JOURNAL ARTICLE

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

