Inhibitory and inducing effects of denzimol on carbamazepine metabolism in the rat.

In vivo and in vitro alterations in carbamazepine (CBZ) metabolism and the extent of enzyme induction of the hepatic cytochrome P-450 system after chronic oral denzimol to rats were evaluated. No effect on drug-metabolizing enzymes was detected for this new anticonvulsant drug at a dose of 15 mg/kg, which is just above the anticonvulsive dose. At higher doses (60 mg/kg) denzimol significantly raised the hepatic cytochrome P-450 content, enhanced CBZ clearance and tend to shorten its elimination t1/2 and that of its active metabolite. These results, combined with those of a previous study showing impairment of CBZ metabolism after single doses of denzimol, suggest that the drug may have either inductive or inhibitory effects on microsomal mixed-function oxidase activity in the rat, depending on the dose and schedule of treatment.