Bioavailability and central side effects of different carbamazepine tablets

Abstract

The bioavailability and central side effects of five carbamazepine tablets with different rates of absorption were investigated in nine healthy volunteers in a randomized cross-over study using single doses of 400 mg. There were seven-fold differences in the peak times (Tmax), 1.5-fold differences in the peak serum concentrations (Cmax) but no significant differences in the total bioavailability (AUC0-96 h) of these tablets. On the tablets with the slowest absorption the serum concentrations were still, 24 h after the ingestion, more than 90% of the Cmax. Central side effects (dizziness, ataxia) were significantly (p less than 0.01) more common when a brand of tablets with a rapid absorption was used. These tablets were characterized by a rapid dissolution in vitro in 0.1 N HCl. The total bioavailability of carbamazepine does not decrease despite moderate prolongation of the absorption phase. The pure AUC-data alone are inadequate to characterize the clinical equivalency of carbamazepine products. Formulations with a slow absorption may be preferable: central side effects are less common and serum concentrations more constant.