Evolution of Regulatory and Scientific Paradigms for Establishing Equivalence of Systemic Exposure from Orally Inhaled Drugs: Current Status and Possible Challenges
Singh GP.
Respiratory Drug Delivery 2010. Volume 1, 2010: 249-260.
Abstract:
Pharmacokinetic (PK) studies play an important role in the development and regulatory evaluation of drugs. Equivalence of systemic exposure based on PK data has been accepted as the basis for documentation of in vivo bioequivalence of drug products which depend upon the systemic circulation to deliver the active moiety(ies) to the target site(s). However, the use of PK approaches for the determination of bioequivalence of locally acting inhaled drugs has evolved at a relatively slow pace, and PK data alone are not considered adequate to support bioequivalence. In the US, PK data are not accepted as evidence for pulmonary delivery, due to entry of drugs into the systemic circulation from both pulmonary and non-pulmonary routes. The apparent lack of unequivocal evidence for lung-specific absorption based on drug levels in the systemic circulation remains the principal hurdle in acceptance of PK evaluations as the sole determinant of in vivo bioequivalence of locally acting inhaled drugs. In addition, the PK studies do not provide evidence for regional distribution within the lung which may be important for clinical response. Further studies and regulatory deliberations are warranted for acceptance of PK data as the “sole” indicator of in vivo bioequivalence of inhaled drugs.
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