Comparative bioavailability of carbamazepine from two slow-release preparations

Abstract

In order to compare the multiple-dose bioavailability of carbamazepine (CBZ) from 2 slow-release preparations, Neurotol slow and Tegretol Retard, a single-blind, randomized, cross-over study was carried out. 21 adult patients with epilepsy were enrolled in the study. At the end of both 2-week treatment periods, a blood sample series was drawn after the administration of the morning CBZ dose. The serum concentrations of CBZ, CBZ-10,11-epoxide (CBZE) and 10,11-dihydro-10,11-trans-dihydroxy-CBZ (CBZD) were measured using HPLC. The mean bioavailability of CBZ from Neurotol slow was 11% (P = 0.002) higher than from Tegretol Retard. Owing to the better bioavailability, the peak (Cmax), lowest (Cmin) and mean (Css) concentrations of CBZ were also significantly higher during Neurotol slow treatment. Fluctuation of serum CBZ concentrations (Cmax-Cmin/Css, ADCss/AUC0-12h) did not differ significantly between the 2 treatments; neither did tmax. Similar results were obtained with CBZE and CBZD. There were more epileptic seizures on Tegretol Retard than on Neurotol slow, but the difference was not statistically significant. We conclude that there are significant differences in the bioavailability of CBZ from these 2 slow-release preparations.