Maternofetal transfer of phenytoin, p-hydroxy-phenytoin and p-hydroxy-phenytoin-glucuronide in the perfused human placenta

Clin Exp Pharmacol Physiol. 1989 Oct;16(10):789-97. doi: 10.1111/j.1440-1681.1989.tb01517.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipyrine / metabolism
  • Female
  • Humans
  • In Vitro Techniques
  • Male
  • Maternal-Fetal Exchange*
  • Metabolic Clearance Rate
  • Perfusion
  • Phenytoin / analogs & derivatives*
  • Phenytoin / metabolism*
  • Placenta / metabolism*
  • Pregnancy
  • Rats
  • Rats, Inbred Strains
  • Solubility

Substances

  • hydroxyphenytoin
  • 5-phenyl-5-(4-hydroxyphenyl)hydantoin glucuronide
  • Phenytoin
  • Antipyrine