In defense of current concepts and applications of clearance in drug development and therapeutics
Date
2022
Authors
Rowland, M.
Roberts, M.S.
Pang, K.S.
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Journal article
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Drug Metabolism And Disposition, 2022; 50(2):187-190
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Abstract
Clearance is one of the most widely quoted and applied pharmacokinetic concepts in drug development and therapy. Its foundations and associated models of drug elimination are well embedded and accepted within the scientific community. Recently, however, the prevailing views that have held us in good stead for the past almost 50 years have been challenged with the argument that organ clearance should not be based on elimination rate, now defined by loss across the liver divided by incoming or systemic concentration, as in current practice, but rather, by the mean concentration of drug within the blood in the organ, which is model-dependent. We argue that all needed parameters already exist, and that the proposed new approach to organ clearance is confusing and unnecessary.
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Copyright 2022 The American Society for Pharmacology and Experimental Therapeutics