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

• Published in: Clinical pharmacology in drug development 2022-03, Vol.11 (3), p.318-323
• Main Authors: Piñeyro‐Garza, Everardo, Gómez‐Silva, Magdalena, Gamino, María E., Delgado‐Roche, Livan
• Format: Article
• Language: English
• Subjects: Bioavailability; Bioequivalence; Drug dosages; Drug therapy; dutasteride; generics; tamsulosin
• ISSN: 2160-763X; 2160-7648
• DOI: 10.1002/cpdd.1011

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®.