Demonstrating Bioequivalence Using Pharmacokinetics: Theoretical Considerations Across Drug Classes
Goyal N, Hochhaus G.
Respiratory Drug Delivery 2010. Volume 1, 2010: 261-272.
Abstract:
Pharmacokinetic (PK) studies, if useful for the assessment of the topical bioequivalence of orally inhaled products (OIPs), need to confirm that the dose available to the lung, the pulmonary residence time and the regional lung deposition for the test and reference formulations are equivalent. Clinical trial simulations suggest that PK studies for drugs with negligible oral bioavailability, or performed under conditions that block oral absorption, should be able to determine the dose available to the lung and the pulmonary residence time. Furthermore, PK simulations may be able to discriminate regional deposition for some drug classes. Differences in the regional deposition of slowly dissolving drugs appear to be reflected in differences in AUC, as slowly dissolving particles are considered to be removed more efficiently from the central part of the lung via mucociliary clearance. Differences in the absorption rate from the central and peripheral airways for rapidly dissolving drugs may also provide an alternative approach to detect regional deposition differences, but requires further evaluation. These simulations, together with supporting evidence from the literature, advocate that PK approaches may address the relevant questions associated with pulmonary bioequivalence for a wide range of OIPs, in general with greater resolution than the currently evaluated clinical tools.
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