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Predicting drug–drug interactions by electrochemically driven cytochrome P450 3A4 reactions

  • Victoria V. Shumyantseva EMAIL logo , Polina I. Koroleva , Tatiana V. Bulko , Gennady V. Sergeev and Sergei A. Usanov
Published/Copyright: December 6, 2021
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Drug Metabolism and Personalized Therapy
From the journal Drug Metabolism and Personalized Therapy Volume 37 Issue 3

Abstract

Objectives

Human cytochrome P450 3A4 is the most abundant hepatic and intestinal Phase I enzyme that metabolizes approximately 60% marketed drugs. Simultaneous administration of several drugs may result in appearance of drug–drug interaction. Due to the great interest in the combination therapy, the exploration of the role of drug as “perpetrator” or “victim” is important task in pharmacology. In this work the model systems based on electrochemically driven cytochrome P450 3A4 for the analysis of drug combinations was used. We have shown that the analysis of electrochemical parameters of cytochrome P450 3A4 and especially, potential of the start of catalysis, Eonset, possess predictive properties in the determination of the leading (“perpetrator”) properties of drug. Based on these experimental data, we concluded, that the more positive potential of the start of catalysis, Eonset, the more pronounced the role of drug as leading medication.

Methods

Electrochemically driven cytochrome P450 3A4 was used as probe and measuring tool for the estimation of the role of interacting drugs.

Results

It is shown that the electrochemical non-invasive model systems for monitoring the catalytic activity of cytochrome P450 3A4 can be used as prognostic devise in assessment of drug/drug interacting medications.

Conclusions

Cytochrome P450 3A4 activity was studied in electrochemically driven system. Method was implemented to monitor drug/drug interactions. Based on the obtained experimental data, we can conclude that electrochemical parameter such as potential of onset of catalysis, Eonset, has predictive efficiency in assessment of drug/drug interacting medications in the case of the co-administration.

Keywords: cytochrome P450 3A4; diclofenac; drug–drug interactions; electrocatalysis; electrochemical parameters; erythromycin; prediction
Corresponding author: Victoria V. Shumyantseva, Institute of Biomedical Chemistry, Moscow 119121, Russia; and Pirogov Russian National Research Medical University, Moscow, Russia, E-mail:

  1. Research funding: This work was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers “Digital biodesign and personalized healthcare” No. 75-15-2020-913.

  2. Author contributions: All the authors have accepted responsibility for the entire of this manuscript and approved this submission.

  3. Competing interests: The funding organization played no role in the study design; in the collection, analysis and interpretation of data; in the writing of this manuscript, or in the decision to submit the manuscript for publication.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The local Institutional Review Board deemed the study exempt from review.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/dmpt-2021-0116).

Received: 2021-02-26
Accepted: 2021-08-31
Published Online: 2021-12-06

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/dmpt-2021-0116
Keywords for this article
cytochrome P450 3A4; diclofenac; drug–drug interactions; electrocatalysis; electrochemical parameters; erythromycin; prediction

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Genotype-based chemotherapy for patients with gastrointestinal tumors: focus on oxaliplatin, irinotecan, and fluoropyrimidines
  4. Factors influencing methotrexate and methotrexate polyglutamate in patients with rheumatoid arthritis: a systematic review of population pharmacokinetics
  5. Original Articles
  6. Predicting drug–drug interactions by electrochemically driven cytochrome P450 3A4 reactions
  7. Evaluation of the stability of furosemide in tablet form during six-month storage in spaceflight and peculiarities of its pharmacokinetics and pharmacodynamics under conditions of anti-orthostatic hypokinesia
  8. CYP450 2D6 and 2C19 genotypes in ADHD: not related with treatment resistance but with over-representation of 2C19 ultra-metabolizers
  9. The markers of the organic acidemias and their ratios in healthy neonates in Serbian population
  10. Kolaviron ameliorates chronic unpredictable mild stress-induced anxiety and depression: involvement of the HPA axis, antioxidant defense system, cholinergic, and BDNF signaling
  11. The efficacy of topical Marham-e-Akbar in chronic atopic dermatitis – an open-label interventional study
  12. In vitro metabolic biomodulation of irinotecan to increase potency and reduce dose-limiting toxicity by inhibition of SN-38 glucuronide formation
  13. Datura stramonium abrogates depression- and anxiety-like disorders in mice: possible involvement of monoaminergic pathways in its antidepressant activity
  14. Synergistic anti-cancer effects of Nigella sativa seed oil and conventional cytotoxic agent against human breast cancer
  15. Short Communication
  16. MTHFR c.665C>T guided fluoropyrimidine therapy in cancer: gender-dependent effect on dose requirements
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