Drug-Metabolizing Cytochrome P450 Enzymes Have Multifarious Influences on Treatment Outcomes

Clin Pharmacokinet. 2021 May;60(5):585-601. doi: 10.1007/s40262-021-01001-5. Epub 2021 Mar 16.


Drug metabolism is a critical process for the removal of unwanted substances from the body. In humans, approximately 80% of oxidative metabolism and almost 50% of the overall elimination of commonly used drugs can be attributed to one or more of various cytochrome P450 (CYP) enzymes from CYP families 1-3. In addition to the basic metabolic effects for elimination, CYP enzymes in vivo are capable of affecting the treatment outcomes in many cases. Drug-metabolizing CYP enzymes are mainly expressed in the liver and intestine, the two principal drug oxidation and elimination organs, where they can significantly influence the drug action, safety, and bioavailability by mediating phase I metabolism and first-pass metabolism. Furthermore, CYP-mediated local drug metabolism in the sites of action may also have the potential to impact drug response, according to the literature in recent years. This article underlines the ability of CYP enzymes to influence treatment outcomes by discussing CYP-mediated diversified drug metabolism in primary metabolic sites (liver and intestine) and typical action sites (brain and tumors) according to their expression levels and metabolic activity. Moreover, intrinsic and extrinsic factors of personal differential CYP phenotypes that contribute to interindividual variation of treatment outcomes are also reviewed to introduce the multifarious pivotal role of CYP-mediated metabolism and clearance in drug therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cytochrome P-450 Enzyme System*
  • Humans
  • Liver
  • Microsomes, Liver
  • Pharmaceutical Preparations*
  • Treatment Outcome


  • Pharmaceutical Preparations
  • Cytochrome P-450 Enzyme System