Bioequivalence of tolbutamide-containing tablet preparations

The present crossover study was undertaken to investigate in 22 volunteers (15 males, 7 females, aged 22-28 years) whether the 2 tolbutamide preparations (tolbutamide R.A.N. vs. rastinon Hoechst) are bioequivalent. After administering a single dose of one 1 g tablet of each preparation the plasma tolbutamide concentration was measured by HPLC over a time-period of 48 hours. The mean AUC0-48 values are nearly identical (998.42 vs. 997.73 micrograms x h x ml-1), while the Cmax values (51.1 vs. 58.8 micrograms/ml) and the tmax values (4.55 vs. 3.82 h) show slight differences. The Westlake intervals claimed to prove bioequivalence lies in the 95% confidence interval between the limits 0.972 and 1.046 (AUC), 0.896 and 0.978 (Cmax), and 0.056 and 1.346 (tmax). For example, this is the result of the parametric analysis considering the randomization. In the case of the parameters of the multiplicative model (AUC and Cmax) the probability of correctly concluding bioequivalence (power) between the 2 preparations reaches 2.0. Regarding maintenance therapy it is of minor importance that the maximum plasma tolbutamide concentrations is 0.7 h later observed with the test preparation than with the standard. The results of this study allow the conclusion that the 2 tablet preparations are bioequivalent.