Tamsulosin is an a1-adrenoceptor antagonist used for the treatment of lower urinary tract symptoms that are suggestive of benign prostatic hyperplasia. It is mostly used in modified-release (MR) formulations. This study was performed to assess the effect of food on the pharmacokinetics of two tamsulosine products in healthy subjects. A randomized single dose (0.4 mg capsules), two-way crossover study was performed in a fasting state or after a high-fat breakfast. Prior to the in vivo study, an in vitro comparative dissolution test was performed. Level A IVIVC was assesed to serve as a surrogate for in vivo bioavailability and to support biowaivers. The plasma samples drawn from the volunteers were analyzed utilizing a sensitive LC-MS-MS method and the bioequivalence between the two drug products was assessed by statistical analysis of the log transformed mean ratios of Cmax, AUC(0-t) and AUC(0-8). There were no serious or unexpected adverse events during the course of this study, with most events reported in comparable numbers of fed and fasted subjects. The bioequivalence of tamsulosine was similar with or without food, with 90% confidence intervals of 91% to 124.4 %, 86.7% to 123.6% and 84.2% to 124.7% for ln (Cmax), ln (AUC 0-48) and ln (AUC0-8), respectively. The fast state study showed a significant higher Cmax associated with insignificant shorter Tmax compared to the fed results (p<0.05). Level A IVIVC showed good point-to-point relationship in both fast and fed state for test and reference products with regression coefficient of 0.96 to 0.98 and 0.99, respectively.
Loading....