Inflammation Suppresses Patients' Ability to Metabolize Cytochrome P450 Substrate Drugs.

Abstract

To assess the impact of inflammation on cytochrome P450 (CYP) drug metabolism in human subjects. 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)). Narrative review of human studies assessing the impact of inflammation or inflammatory suppression with biologic drugs on CYP drug metabolism were used. 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. 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. Like other types of drug-drug or drug-disease interactions, inflammation can alter the steady-state concentration of CYP metabolized drugs.