Assessment of metabolites in bioequivalence studies: should bioequivalence criteria be applied on the sum of parent compound and metabolite?

The objective of this study was to demonstrate the impact of the sum of parent compound and metabolite in bioequivalence assessment. Four drugs with active metabolite were selected to assess bioequivalence. Bioequivalence criteria of 80 - 125% were applied to the parent compound, the metabolite, and the sum of parent compound and metabolite. The results indicated that the application of 80 - 125% bioequivalence criteria to the sum of parent compound and metabolite might be misleading. The 90% confidence interval should be applied separately to the parent compound and each metabolite.