Abstract
Our knowledge of the roles of individual cytochrome P450 (P450) enzymes in drug metabolism has developed considerably in the past 30 years, and this base has been of considerable use in avoiding serious issues with drug interactions and issues due to variations. Some newer approaches are being considered for “phenotyping” metabolism reactions with new drug candidates. Endogenous biomarkers are being used for noninvasive estimation of levels of individual P450 enzymes. There is also the matter of some remaining “orphan” P450s, which have yet to be assigned reactions. Practical problems that continue in drug development include predicting drug-drug interactions, predicting the effects of polymorphic and other P450 variations, and evaluating interspecies differences in drug metabolism, particularly in the context of “metabolism in safety testing” regulatory issues [“disproportionate (human) metabolites”].
Significance Statement Cytochrome P450 enzymes are the major catalysts involved in drug metabolism. The characterization of their individual roles has major implications in drug development and clinical practice.
Footnotes
- Received March 26, 2024.
- Revision received May 28, 2024.
- Accepted July 22, 2024.
Recent work in this laboratory has been supported in part by National Institutes of Health National Institute of General Medical Sciences [Grant R01 GM118122]. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author and do not necessarily reflect the views of the National Institutes of Health.
The author has no conflict of interest to declare.
- Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics
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