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On Assessment of Bioequivalence for Drugs with Negligible Plasma Levels
Author(s) -
Liu JenPei,
Chow SheinChung
Publication year - 1993
Publication title -
biometrical journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 63
eISSN - 1521-4036
pISSN - 0323-3847
DOI - 10.1002/bimj.4710350111
Subject(s) - bioequivalence , pharmacokinetics , medicine , crossover study , bioavailability , bronchospasm , plasma concentration , pharmacology , drug , mathematics , asthma , alternative medicine , pathology , placebo
In 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.