The presence of inflammation can significantly affect the steady-state concentration of medications metabolized by cytochrome P450 (CYP) enzymes, according to the findings of a narrative review of human studies recently published in Annals of Pharmacotherapy.

C. Michael White, PharmD, from the University of Connecticut School of Pharmacy, searched PubMed from 1980 to July 2021 to obtain studies analyzing the impact inflammation has on CYP drug metabolism in healthy patients as well as those with various diseases.

Suppressed drug metabolism was identified in patients with various inflammatory conditions including infection, critical illness, and cancer. Findings revealed that inflammatory markers such as C-reactive protein and α-1-acid glycoprotein were associated with a reduction in the clearance of medications metabolized by CYP3A4, CYP1A2, and CYP2C19.

An association was also observed between increased interleukin-6 concentrations and reduced clearance for CYP3A4 and CYP2C19 substrates. The relationship between CYP2D6 metabolism and inflammation could not be ascertained due to insufficient data.


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Based on these findings, White concluded that “the onset or resolution of a new inflammatory phenomenon should necessitate more judicious patient monitoring to prevent adverse events or loss of efficacy in patients with narrow therapeutic index drugs.”

Reference

White CM. Inflammation suppresses patients’ ability to metabolize cytochrome P450 substrate drugs. Ann Pharmacother. Published online September 30, 2021. doi.org/10.1177/10600280211047864.