Maternofetal transfer of phenytoin, p-hydroxy-phenytoin and p-hydroxy-phenytoin-glucuronide in the perfused human placenta.
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.
Dickinson
R G
RG
Department of Medicine, University of Queensland, Royal Brisbane Hospital, Herston, Australia.
Fowler
D W
DW
Kluck
R M
RM
D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008431:Maternal-Fetal Exchange; D008657:Metabolic Clearance Rate; D010477:Perfusion; D010672:Phenytoin / Q000031:analogs & derivatives* / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility
C001419:hydroxyphenytoin; C030590:5-phenyl-5-(4-hydroxyphenyl)hydantoin glucuronide; D010672:Phenytoin; D000983:Antipyrine