The Clinical Utility of Pharmacokinetics in Demonstrating Bioequivalence of Locally Acting Orally Inhaled Drugs
Daley Yates PT.
Respiratory Drug Delivery 2010. Volume 1, 2010: 273-284.
Abstract:
There is a lack of established robust bioequivalence (BE) methodology for locally acting orally inhaled drugs. The suitability of pharmacokinetic (PK) methods to demonstrate BE is currently being explored. PK data from clinical studies that inform this debate have been reviewed. Examples are presented where, based on PK data, BE was concluded, partially concluded and not concluded. The robustness of these conclusions and the extent to which PK data correlate with in vitro fine particle mass (FPM) and clinical efficacy data are explored. When test and reference inhalers were available in multiple strengths, it was not always possible to extrapolate the BE conclusions to all dose strengths. There was also a lack of data to determine whether BE between two inhalers can be extrapolated from one patient population to another e.g., from asthma to COPD, despite documented differences in pulmonary pathophysiology and the pharmacological sites of action. Although the theoretical arguments to use PK data may be compelling, the experimental evidence that PK data are a suitable surrogate for topical efficacy is less convincing. Nevertheless, PK data have an important role to play in assessing BE, particularly in evaluating systemic safety and in vivo inhaler performance, and should be included as part of a package including; device comparability, in vitro performance, patient use and efficacy evaluations in the appropriate patient population.
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