Biomol Ther (Seoul). 2021 Sep 03; doi: 10.4062/biomolther.2021.102. Epub 2021 Sep 03.

Inhibition of Cytochrome P450 Enzymes by Drugs-Molecular Basis and Practical Applications.

Biomolecules & therapeutics

F Peter Guengerich

PMID: 34475272 DOI: 10.4062/biomolther.2021.102

Abstract

Drug-drug interactions are a major cause of hospitalization and deaths related to drug use. A large fraction of these is due to inhibition of enzymes involved in drug metabolism and transport, particularly cytochrome P450 (P450) enzymes. Understanding basic mechanisms of enzyme inhibition is important, particularly in terms of reversibility and the use of the appropriate parameters. In addition to drug-drug interactions, issues have involved interactions of drugs with foods and natural products related to P450 enzymes. Predicting drug-drug interactions is a major effort in drug development in the pharmaceutical industry and regulatory agencies. With appropriate in vitro experiments, it is possible to stratify clinical drug-drug interaction studies. A better understanding of drug interactions and training of physicians and pharmacists has developed. Finally, some P450s have been the targets of drugs in some cancers and other disease states.

Keywords: CYP; Cytochrome P450; Drug-drug interactions; Enzyme inhibition; P450 inhibition

Publication Types

• Journal Article

Grant support

• R01 GM118122/GM/NIGMS NIH HHS/United States