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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

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.


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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