Bioequivalence Between Two Fixed Dose Combinations of Dutasteride and Tamsulosin in Male Subjects Under Fasting and Fed Conditions

The bioavailability of two fixed dose combination of dutasteride 0.5 mg and tamsulosin hydrochloride 0.4 mg was compared in two single-dose, randomized, open-label, 2-way, crossover bioequivalence studies with 52 Brazilian healthy male subjects. One study was under fasting conditions and the other one after a standard breakfast. Blood samples were taken predose and up to 96 h postdose and obtained plasma was frozen and kept until analysis. Plasmatic concentrations of dutasteride and tamsulosin were determined simultaneously using a validated UPLC-MS/MS method. Chromatographic separation was achieved with the chromatographic column UPLC BEH C18 and total run time was 3 minutes. Confidence intervals (CI90%) for the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC0-t) were calculated with log-transformed data. In the fasting bioequivalence study, the ratios and 90% CI for the geometric mean of dutasteride were 99.26% (93.07-105.86%) for Cmax and 102.49% (96.86-108.45%) for AUC0-t and the ratios and 90% CI for the geometric mean of tamsulosin were 102.39% (98.13-106.83%) for Cmax and 108.83% (102.49-115.57%) for AUC0-t. In the fed bioequivalence study, the ratios and 90% CI for the geometric mean of dutasteride were 92.42% (86.08-99.23%) for Cmax and 102.82% (98.73-107.08%) for AUC0-t and the ratios and 90% CI for the geometric mean of tamsulosin were 96.26% (89.86-103.11%) for Cmax e 95.88% (90.31-101.8%) for ASC0-t. At fasting and fed conditions, the test and reference formulations were considered bioequivalent since the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125% (ANVISA).