Bioequivalence Assessment of an Oral Fixed-Dose Formulation of Dutasteride-Tamsulosin 0.5 mg/0.4 mg: A Randomized, Single-Blind, Single-Dose, 2-Period Crossover Study in Mexican Population Under Fasted Conditions.

Abstract

The aim of the present study was to compare the bioavailability and to demonstrate the bioequivalence between a dutasteride-tamsulosin 0.5 mg/0.4 mg capsule formulation and the regulatory reference drug (Combodart®, GlaxoSmithKline). A randomized, single-blind, single-dose, 2-way crossover study under fasting conditions, with at least a 28-day washout period was carried out in healthy volunteers. Plasma concentrations of drugs were determined by high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic analysis included maximum plasma concentration (Cmax ), area under the plasma concentration-time curve (AUC) from time 0 to 72 hours, and AUC from baseline to infinity. The test formulation was considered bioequivalent if the geometric mean ratios (test/reference) were within the predetermined range of 80% to 125%. Safety and tolerability were evaluated by clinical assessment. The confidence intervals for the log-transformed test/reference ratios for dutasteride, Cmax (95.4-109.2) and AUC from baseline to 72 hours (93.2-109.1), and for tamsulosin, Cmax (101.9-119.8), AUC from baseline to the last quantifiable concentration (91.4-106.3) and AUC from baseline to infinity (90.9-103.3), were within the allowed limit specified by the regulatory authorities (80%-125%). In addition, both test and reference drugs were safe and tolerated. These results demonstrated the bioequivalence of test product (Dakart®) compared with Combodart®.