Effect of anticonvulsants on in vitro prothrombin synthesis in adult and fetal rat liver

Abstract

Prothrombin synthesis in a postmitochondrial supernatant fraction of rat liver from vitamin K-deficient rats was unchanged in the presence of 10 −3 m concentrations of phenobarbital, phenytoin, or primidone. Warfarin (10 −5 m) significantly decreased prothrombin synthesis with 4.4 X 10 −7 or 2.2 × 10 −6 m vitamin K added to the incubation medium whereas phenytoin (10 −3 m) had no affect. Pretreatment of vitamin K-deficient adult male rats for 2 days with phenobarbital (80 mg/kg), phenytoin (200 mg/kg), or primidone (200 mg/kg) did not alter in vitro prothrombin synthesis. Pregnant vitamin K-deficient rats were treated from the 14th to 20th day of gestation with 100 mg/kg phenytoin or 80 mg/kg phenobarbital. Although the fetuses contained significant quantities of phenytoin (95.4 ± 37.5 μg/ml serum) or phenobarbital (32.25 ± 4.51 μg/ml serum), prothrombin synthesis by fetal liver was unaffected. Feeding a diet deficient in both vitamin K and folic acid to pregnant rats treated with phenytoin (100 mg/kg) also did not alter prothrombin synthesis but appeared to increase fetal accumulation of phenytoin (289 ± 109.9 μg/ml serum).