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MATERNOFETAL TRANSFER OF PHENYTOIN, p ‐HYDROXY‐PHENYTOIN AND p ‐HYDROXY‐PHENYTOIN‐GLUCURONIDE IN THE PERFUSED HUMAN PLACENTA
Author(s) -
Dickinson R. G.,
Fowler D. W.,
Kluck R. M.
Publication year - 1989
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1989.tb01517.x
Subject(s) - phenytoin , transplacental , lipophilicity , chemistry , glucuronide , metabolite , conjugate , anticonvulsant , pharmacology , placenta , endocrinology , fetus , medicine , pregnancy , stereochemistry , epilepsy , biochemistry , biology , mathematical analysis , mathematics , psychiatry , genetics
SUMMARY 1. Transplacental transfer of the anti‐epileptic agent phenytoin (PHT), its phase I metabolite, p ‐hydroxy‐phenytoin ( p ‐OH‐PHT), and its phase II conjugate p ‐OH‐PHT‐glucuronide, was studied in term placental lobules perfused single pass in both maternal and fetal circuits. 2. Ratios of clearance of PHT, p ‐OH‐PHT and p ‐OH‐PHT‐glucuronide to clearance of antipyrine were 1.08 ± 0.03, 0.52 ± 0.02 and 0.12 ± 0.01 (mean and s.e.m.), respectively. 3. Transfer was positively correlated with lipophilicity as measured by the apparent partition coefficient determined between octanol and pH 7.4 buffer.