Inflammation Suppresses Patients' Ability to Metabolize Cytochrome P450 Substrate Drugs

Ann Pharmacother. 2022 Jul;56(7):809-819. doi: 10.1177/10600280211047864. Epub 2021 Sep 30.

Abstract

Objective: To assess the impact of inflammation on cytochrome P450 (CYP) drug metabolism in human subjects.

Data sources: A PubMed search was done from 1980 to July 2021 limited to human subjects and English language using a search strategy of (((phase I metabolism) OR (CYP) OR (cytochrome P450)) AND (inflammatory OR inflammation)).

Study selection and data extraction: Narrative review of human studies assessing the impact of inflammation or inflammatory suppression with biologic drugs on CYP drug metabolism were used.

Data synthesis: Patients with inflammatory conditions ranging from fungal, viral, or bacterial infections to noninfectious causes (critical illness, surgical procedure, cancer, or transplantation of stem cells or organs) have suppressed drug metabolism. Markers of inflammation such as C-reactive protein or α-1-acid glycoprotein are correlated with reduced clearance through CYP3A4, CYP1A2, and CYP2C19. Elevated interleukin-6 concentrations are also associated or correlated with reduced clearance for CYP3A4 and CYP2C-19 isoenzymes. There was insufficient information to properly assess CYP2D6.

Relevance to patient care and clinical practice: Health professionals should appreciate that patients with acute or chronic inflammation from infectious or noninfectious causes could have suppressed drug metabolism through CYP3A4, CYP1A2, and CYP2C19. For narrow therapeutic index drugs, such as many of the drugs assessed in this review, that means more judicious drug monitoring to prevent adverse events.

Conclusions: Like other types of drug-drug or drug-disease interactions, inflammation can alter the steady-state concentration of CYP metabolized drugs.

Keywords: drug interactions; inflammation; metabolism.

Publication types

  • Review

MeSH terms

  • Cytochrome P-450 CYP1A2* / metabolism
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A*
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Interactions
  • Humans
  • Inflammation / drug therapy

Substances

  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A