ELEVATION OF PLASMA CARBAMAZEPINE CONCENTRATIONS BY KETOCONAZOLE IN PATIENTS WITH EPILEPSY

The effect of ketoconazole (200 mg/d orally for 10 days) on the plasma concentrations of carbamazepine (CBZ) and its active metabolite carba mazepine-10,11-epoxide (CBZ-E) was assessed in eight patients with epi lepsy stabilized on CBZ therapy. Administration of ketoconazole was as sociated with a significant increase in plasma CBZ concentrations (fro m 5.6 +/- 1.9 to 7.2 +/- 2.9 mu g/ml on day 10 [means +/- SD, P < 0.02 ]), whereas plasma concentrations of CBZ-E were unchanged. After ketoc onazole was discontinued, plasma CBZ levels decreased to pretreatment values. This interaction was probably mediated by an inhibiting action of ketoconazole on cytochrome CYP3A4, the main enzyme responsible for CBZ metabolism.