DefinePK

Abstract

The bioequivalence of two brands of clobazam 10 mg tablets was demonstrated in this study. A single dose was carried out in 14 healthy volunteers with a two-sequence, crossover block-randomized design. Blood samples were taken prior to each administration and at 18 points within 72 h after the dose administration. Plasma concentrations of clobazam and N-desmethylclobazam were determined by HPLC method. The pharmacokinetic parameters, Cmax and Tmax were obtained directly from plasma concentration-time profiles. ke was estimated by log-linear regression and AUC was calculated by the linear trapezoidal rule for both clobazam and N-desmethylclobazam. The pharmacokinetic parameters, AUC(0-t), AUC(0-∞) and Cmax were tested for equivalence after logtransformation of data. Differences of Tmax were evaluated by a non-parametric test. The 90% confidence intervals of the mean values for the test/reference ratios were 94-103% for AUC(0-t), 90-110% for AUC(0-∞) and 87-109% for Cmax, which were within the acceptable bioequivalence limits of 80-125% for clobazam. Based on desmethylclobazam data, the 90% confidence interval for AUC(0-t) and Cmax were calculated to be 82-106% and 81-117% respectively. Therefore two formulations were considered bioequivalent.