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

Abstract

The estimated point and the 90% confidence intervals were 91.07% (84.54-98.11%) for AUC and 91.43% (84.65-98.75%) for AUC, that is, within the ranges for acceptance of bioequivalence. The intra-subject variability's were 11.45% for AUC and 11.87% for AUC 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) approach could be considered for bioequivalence assessment for dutasteride.

Evaluation of Truncated AUC as an Alternative Measure to Assess Pharmacokinetic Comparability in Bridging Biologic–Device Using Prefilled Syringes and Autoinjectors

“…For small molecules with a long elimination half‐life, it is well‐accepted to use tAUC in lieu of AUC 0–inf , given that the tAUC can cover the complete absorption phase 7 . The utility of tAUC has also been demonstrated in several clinical and modeling and simulation studies of small‐molecule drugs 45–51 . Our study demonstrated that to bridge the PFS and AI , tAUC evaluated until day 28 post‐dose can achieve high concordance (≥85%) for biologics that exhibit linear or nonlinear elimination with k a values greater than or equal to 0.1/day and with a typical sample size of 70 subjects per arm.…”

“…7 The utility of tAUC has also been demonstrated in several clinical and modeling and simulation studies of smallmolecule drugs. [45][46][47][48][49][50][51] Our study demonstrated that to bridge the PFS and AI , tAUC evaluated until day 28 post-dose can achieve high concordance (≥85%) for biologics that exhibit linear or nonlinear elimination with k a values greater than or equal to 0.1/day and with a typical sample size of 70 subjects per arm. tAUC 0-28 could be used appropriately to evaluate PK comparability between the two presentations, even for biologics with a long elimination half-life of 40 days, to reduce the study duration compared with an evaluation of AUC 0-inf .…”