The effect of pregnancy on the metabolism of [14C]phenytoin in the isolated perfused rat liver.

The metabolism of [14C]phenytoin (DPH) was measured in isolated perfused livers from non-pregnant female rats and rats at 13, 15, 17, 19 and 21 days of gestation. The half-life of [14C]phenytoin in the perfusate was not significantly altered by pregnancy in livers perfused with 20% blood at 2 ml/min/g of liver but was increased from 38 min in control livers to 158 min in livers from rats at 21 days of gestation when livers were perfused with 10% blood at 1 ml/min/g of liver. Secretion of the glucuronide conjugate of 5-[14C]phenyl-5-parahydroxy-phenylhydantoin into the bile was markedly inhibited during the latter stages of pregnancy such that a 4-fold decrease in the cumulative secretion into the bile was present at 21 days of gestation. The bile/perfusate concentration ratio of the glucuronide after 30 min was 148 in control livers but decreased to 6 in livers from rats at 21 days gestation.