EFFECT OF MULTIPLE-DOSE OMEPRAZOLE ON THE PHARMACOKINETICS OF CARBAMAZEPINE

The pharmacokinetics of carbamazepine (CBZ) were studied in 7 patients with duodenal ulcer both before and after 14 days' treatment with omeprazole (20 mg/day), as this substituted benzimidazole has been shown to alter the pharmacokinetics of some drugs. CBZ serum levels were determined by high pressure liquid chromatography following oral administration of CBZ 400mg. Omeprazole treatment caused increases in CBZ blood levels and significantly prolonged the elimination half-life from 17.2 +/- 5.9 hours to 37.3 +/- 22.8 hours. Simultaneously, there was an increase in the area under the curve (AUC(0).(infinity) from 382.3 +/- 81.1 mu g/ml.h to 668.8 +/- 241.6 mu g/ml.h, while the CBZ clearance was decreased significantly from 20.7 +/- 3.4 ml/h/kg to 12.5 +/- 3.5 ml/h/kg. Other parameters such as maximum plasma drug concentration (C-max), time to reach maximum concentration (t(max)), and apparent volume of distribution at steady-state (V-ss) were, however, not altered by omeprazole treatment. The reduction in clearance and increase in half-life and AUC(0.infinity), values may be attributed to inhibition of CBZ oxidative metabolism by omeprazole.