Bioequivalence and intrasubject variability.

Bioequivalence of the two formulations refers to the equivalence of the marginal distributions of the two formulations. Under normal assumptions, this would require the equivalence of both average and intrasubject variability of bioavailability. A procedure is introduced for the equivalence in intrasubject variability for bioavailability/bioequivalence studies with the standard two-by-two crossover design. It is shown that the confidence interval approach is operationally identical to the hypothesis testing in assessment of equivalence of intrasubject variability. A hypothetical data set from a two-by-two crossover bioequivalence study illustrates the procedure.