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Article, Chapter, or Book Title:  Estimating product bioequivalence for highly variable veterinary drugs
Author(s):  Claxton R, Cook J, Endrenyi L, Lucas A, Martinez MN, and Sutton SC.
Year:  2012
Month:  Mar
Journal Abbrev, Book Title, or Conference:  J Vet Pharmacol Therap
Journal Full Name:  Journal of Veterinary Pharmacology and Therapeutics
Volume:  35
Start Page:  11
End Page:  16
Key Words:  pharmacokinetic variability, scaled average bioequivalence, veterinary dosage forms, highly variable veterinary drugs, bioequivalence
Abstract:  The occurrence of drugs and drug formulations associated with large intrasubject pharmacokinetic (PK) variability has been well described in humans and is likewise encountered in veterinary medicine. The scaled average bioequivalence (SABE) approach adopted by CDER of the FDA for the determination of bioequivalence (BE) of highly variable drugs (HVD) needs to be considered when applied to veterinary dosage forms. However, because of some of the unique challenges that are encountered within the framework of veterinary medicine, variations of CDERs approach are presented. The present manuscript discusses HVD and highly variable veterinary drugs (HVVD) from the perspective of possible alternative approaches to support the assessment of product BE in veterinary medicine. Limitations in the use of 3- and 4-way crossover study designs are enumerated. In addition to a need for a statistical analysis of HVVD when using a parallel study design, the use of the secondary criteria (test-to-reference ratio), definition of Ã0, and average BE with expanding limits are raised. A number of the details need to be finalized, from the selection of a regulatory constant to the determination of highly variable in a veterinary drug product. Academicians, industrial scientists, and regulators should continue this discussion and resolve these details.