Bioequivalence of tamsulosin 0.4 mg film-coated sustained-release tablet formulations in healthy subjects under fasting conditions.

Abstract

This open-label, randomized, single-dose, 4-period, 2-sequence, fully replicated study was conducted to evaluate the bioequivalence of tamsulosin 0.4 mg sustained-release film-coated tablet manufactured by PT Dexa Medica, Indonesia, and Harnal OCAS 0.4 mg prolonged-release tablet manufactured by Astellas Pharma Europe B.V., the Netherlands, imported by PT Combiphar, Indonesia, under fasting conditions in 28 healthy adult Indonesian males. Subjects were randomly assigned to receive the test formulation (1 single tablet of 0.4 mg) or the reference formulation (1 single tablet of 0.4 mg) orally in each of the 4 study periods, according to the full replicate design. Therefore, over the 4 complete periods, each subject received 2 administrations of the test formulation and 2 administrations of the reference formulation, with each administration separated by a 7-day washout period. The plasma concentration of tamsulosin from the blood samples was analyzed using validated ultra-performance liquid chromatography with tandem mass spectroscopy detection (UPLC-MS/MS), and pharmacokinetic parameters (AUC_0-t, AUC_0-∞, C_max, t_max, and T_1/2) were calculated. The 90% confidence interval (CI) for the test/reference geometric mean ratio (GMR) of the AUC_0-t was 80.2 - 98.4%, and for AUC_0-∞ it was 80.5 - 120.1%. The 90% CI GMR of C_max was 89.3 - 107.7%. All parameters were within the 90% CI GMR acceptance criteria of 80.0 - 125.0%. The T_1/2 and t_max of the 2 test drugs and the 2 reference drugs were not statistically different. There was no adverse effect observed during the study. Based on the study results, it was concluded that both tamsulosin formulations were bioequivalent and well tolerated.