On Assessment of Bioequivalence for Drugs with Negligible Plasma Levels

Abstract

AbstractIn bioavailability studies, bioequivalence between drug products is usually determined based on some pharmacokinetic responses such as area under the blood or plasma concentration‐time curve and maximum concentration. For some drug products, however, we may have negligible plasma levels because their intended routes of administration. In this case, assessment of bioequivalence between drug products of this kind may be established using clinical endpoints such as therapeutic response and time to the onset of a therapeutic response. In this paper, we propose two procedures which modify the method of generalized estimating equations (Liang and Zeger, 1986) and the proportional hazard models for paired failure times to assess bioequivalence between two drug products under the structure of a standard two‐sequence, two‐period crossover design. An example concerning a bioequivalence trial for albuterol metered dose inhaler indicated for acute bronchospasm (Herson, 1991) is used to illustrate the proposed procedures.