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

Abstract

Purpose To investigate the effect of using truncated area under the curve (AUC_0-72) 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 AUC_0-72 and AUC_0-144.

Results The estimated point and the 90% confidence intervals were 91.07% (84.54–98.11%) for AUC_0-72 and 91.43% (84.65–98.75%) for AUC_0-144, that is, within the ranges for acceptance of bioequivalence. The intra-subject variability’s were 11.45% for AUC_0-72 and 11.87% for AUC_0-144.

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 (AUC_0-72) approach could be considered for bioequivalence assessment for dutasteride.

Key words

benign prostate hyperplasia - LC-MS/MS - pharmacokinetic

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