Mechanisms of cytokine influence on drug pharmacokinetics: the role of the cytochrome P-450 system

Lapshtaeva A.V., Sychev I.V., Puzyakova D.V., Sychev D.A.

1) N.P. Ogarev Mordovia State University, Saransk, Russia; 2) B.V. Petrovsky Russian Scientific Center of Surgery, Moscow, Russia; 3) Russian Medical Academy of Continuous Professional Education, Moscow, Russia

The cytochrome P450 (CYP) system is a superfamily of heme-containing enzymes that play a key role in the metabolism of xenobiotics, including the vast majority of drugs, as well as endogenous compounds (steroids, bile acids, fatty acids). Regulation of CYP activity is a complex process influenced by multiple factors. Proinflammatory cytokines such as interleukin-6, interleukin-1β, tumor necrosis factor-alpha, and interferon-gamma are potent suppressors of the expression and activity of major CYP isoforms. This review examines the molecular mechanisms underlying cytokine-mediated CYP regulation, including the suppression of gene transcription through the JAK-STAT, NF-κB, and MAPK pathways and post-transcriptional modifications, and highlights the clinical significance of this phenomenon. Understanding these mechanisms is essential for personalizing pharmacotherapy and developing new strategies for predicting drug interactions in systemic inflammation. 

For citations: Lapshtaeva A.V., Sychev I.V., Puzyakova D.V., Sychev D.A. Mechanisms of cytokine influence on drug pharmacokinetics: the role of the cytochrome P-450 system. Pharmateca. 2026;33(1):43-49. (In Russ.). DOI: https://dx.doi.org/10.18565/pharmateca.2026.1.43-49

Authors’ contribution: Research concept and design – D.A. Sychev, A.V. Lapshstaeva. Data collection and processing – A.V. Lapshstaeva, D.V. Puzakova, I.V. Sychev. Text writing – A.V. Lapshtaeva, I.V. Sychev. Editing – D.A. Sychev.
Conflicts of interest: The authors confirm that they have no conflicts of interest to declare.
Funding: The study was conducted without any sponsorship.

Keywords

About the Authors

Anna V. Lapshtaeva, Cand. Sci. (Med.), Associate Professor, Department of Immunology, Microbiology, and Virology with a Course in Clinical Immunology and Allergology, N.P. Ogarev Mordovia State University, Saransk, Russia; av_lapshtaeva@mail.ru, ORCID: https://orcid.org/0000-0003-4828-2476, eLIBRARY SPIN: 9138-6257 (corresponding author)
I.V. Sychev, B.V. Petrovsky Russian Scientific Center of Surgery, Moscow, Russia; ORCID: https://orcid.org/0000-0002-6454-2349, eLIBRARY SPIN: 5162-3779
D.V. Puzyakova, N.P. Ogarev Mordovia State University, Saransk, Russia; ORCID: https://orcid.org/0009-0003-3442-1225, eLIBRARY SPIN: 8812-1945
D.A. Sychev, Dr. Sci. (Med.), Professor, Professor of the Russian Academy of Sciences, Academician of the Russian Academy of Sciences, Scientific Director of the World-Class Genomic Research Center «Center for Predictive Genetics, Pharmacogenetics and Personalized Therapy», B.V. Petrovsky Russian Scientific Center of Surgery; Head of the Department of Clinical Pharmacology and Therapy named after Academician B.E. Votchal, Russian Medical Academy of Continuous Professional Education, Moscow, Russia; ORCID: https://orcid.org/0000-0002-4496-3680, eLIBRARY SPIN: 4525-7556

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