Comparative Studies of the Bioequivalence of a Generic (tenolol®)Andtheinnovatoratenolol in Healthy Thai Volunteers

Abstract

Bioequivalence of 50 mg and 100 mg of the generic atenolol tablets (Tenolol®, Siam

Pharmaceutical) were compared to the innovative product (Tenormin®, Zeneca Limited). Each preparation was administered to twelve healthy Thai volunteers according to a randomized balance two-way crossover design with one week washout period. After drug administration, serial blood samples were collected over a period of 24 hr and 30 hr for 50 mg and 100 mg atenolol preparations, respectively. Atenolol plasma concentrations were measured using HPLC technique with fluorometric detection. Pharmacokinetic parameters were analyzed by noncompartrnental pharmacokinetic method using TOPFIT. The means and parametric 90% confidence intervals of the ratio (Tenolol®/Tenormin®) of C_max, and AUC_0-∞ were 1.17 (1.00-1.34) and 1.08 (0.96-1.19), as well as 0.94 (0.77-1.12) and 0.98 (0.84-1.14) for 50 mg and 100 mg doses, respectively. These values complied with the acceptable bioequivalence ranges of 0.7-1.43 and 0.8- 1.25 for the ratios (Test/Reference) of C_max and AUC_0-∞  respectively. The mean differences of T_max (Tenolol®-Tenormin®) were -0.33 and -0.06 hr for 50 mg and 100 mg, respectively. These values were well within the stipulated bioequivalence ranges of Tm" differences (± 20% of the Tm" of the reference formulation) of ± 0.58 hr and ± 0.78 hr for 50 mg and 100 mg preparations, respectively. Based on the result of this study, 50 mg and 100 mg of Tenolol® were bioequivalent to the innovator (Tenormin®) with respect to the extent and rate of absorption.