Impact of Truncated Area on Point Estimate and Intra-Subject Variability in Bioequivalence of Dutasteride with Long Half-Life

Abstract

Abstract Purpose To investigate the effect of using truncated area under the curve (AUC0-72) on bioequivalence of dutasteride with long half-life in point estimate and intra-subject variability. Methods Fifteen subjects were enrolled in this single-dose, open-label, randomized two-way crossover design following an overnight fasting with five-week washout period. Plasma samples were collected to 72 h and 144 h following drug administration and dutasteride were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The pharmacokinetic parameters for bioequivalence assessment were AUC0-72 and AUC0-144. Results The estimated point and the 90% confidence intervals were 91.07% (84.54–98.11%) for AUC0-72 and 91.43% (84.65–98.75%) for AUC0-144, that is, within the ranges for acceptance of bioequivalence. The intra-subject variability’s were 11.45% for AUC0-72 and 11.87% for AUC0-144. Conclusions There was no statistically significant difference in point estimated and intra-subject variability between truncated AUC at 72 h and 144=h and the truncated AUC (AUC0-72) approach could be considered for bioequivalence assessment for dutasteride.