Metabolism of carbamazepine and its epoxide metabolite in human and rat liver in vitro.

The epoxidation of carbamazepine (CBZ) and the hydration of the primary epoxide metabolite was studied in microsomes isolated from ten human livers. To study the epoxide hydrolase activity a high-performance liquid-chromatographic method was developed for the analysis of dihydro-CBZ-trans-diol. There was a pronounced variation between the specimens in the activity of both enzymes. There appeared to be a positive correlation between the activity of the two enzymes. In rats pretreated with either CBZ or phenobarbital for 4 days, the microsomal epoxidation of CBZ was induced. The epoxide hydrolase activity was also increased, although less so than in epoxidation.