Inhibition of carbamazepine and phenytoin metabolism by nafimidone, a new antiepileptic drug.

Abstract

When nafimidone (NFM), a new antiepileptic drug, was given to six patients already taking carbamazepine (CBZ) and phenytoin (PHT) as part of a late phase I pilot efficacy trial, it reduced CBZ elimination by 76-87% and reduced PHT elimination by 38-77%. CBZ and PHT levels rose within 24 h after NFM was started, and began to decline within 12 h after NFM was stopped. The inhibitory effect on CBZ metabolism persisted throughout the course of 1 year of long-term follow-up in all five patients who continued with the drug after completion of the pilot study. Inhibition of PHT elimination persisted in three of the patients, but PHT elimination returned to baseline rates in the other two patients during long-term follow-up. The inhibition of CBZ and PHT metabolism is probably due to binding of cytochrome P-450 by NFM or a metabolite and thus inhibition of the hepatic microsomal mixed-function oxidase system.