Felbamate in vitro metabolism by rat liver microsomes

Incubation of [14C]felbamate at 37 degrees C for 60 min with liver microsomes from untreated Sprague-Dawley rats converted 10% of the drug to the p-hydroxy (6%) and 2-hydroxy (4%) metabolites. With microsomes from phenobarbital-pretreated rats, 21% of the drug was metabolized to the p-hydroxy (7.5%) and 2-hydroxy (13.5%) metabolites. With microsomes from felbamate-pretreated rats, up to 25% of drug was metabolized to the p-hydroxy (5%) and 2-hydroxy (20%) metabolites. In addition, a small amount of the monocarbamate metabolite was also present, but no other metabolites were formed. Coincubations of [14C]phenytoin with felbamate had no effect on the metabolism of phenytoin, whereas the amount of [14C]felbamate metabolized in the presence of phenytoin decreased by 30-38%.