Journal of Bioequivalence & Bioavailability

Abstract

The Role of Metabolite in Bioequivalence Decision Making

Qaisi AM, Tutunji L, Tutunji M and Mohsen MA

Purpose: To investigate whether the combined concentrations of the parent drug and its corresponding metabolite impacts the experimental design of bioequivalence studies.
Methods: Enalpril and sildenafil were selected to assess bioequivalence as both drugs have active metabolites. The bioequivalence study of enalpril was conducted under fasting conditions, while the bioequivalence assessment of sildenafil was conducted under both fasting and fed conditions. For the three studies, the bioequivalence criteria of 80-125% was applied to assess the parent compounds alone, the active metabolites alone, and both the parent drugs and the active metabolites.
Results: Similar statistical results to assess bioequivalence were obtained for the parent drug, metabolite, and the sum of the parent drug and metabolite for AUC. In the case of Cmax, the intra subject variability of the bioequivalence statistical results with regards to the metabolite and the sum of the parent and the metabolite was lower than that for the parent drug while the power of the bioequivalence decision was higher for the metabolite and the sum of the parent drug and the metabolite.
Conclusions: An improved intra subject variability resulted in higher power with a smaller sample size in the Cmax values with regards to decision making in bioequivalence studies.