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Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

Editor-in-Chief: Llerena, Adrián

Editorial Board: Benjeddou, Mongi / Chen, Bing / Dahl, Marja-Liisa / Devinsky, Ferdinand / Hirata, Rosario / Hubacek, Jaroslav A. / Ingelman-Sundberg, Magnus / Maitland-van der Zee, Anke-Hilse / Manolopoulos, Vangelis G. / Marc, Janja / Melichar, Bohuslav / Meyer, Urs A. / Nair, Sujit / Nofziger, Charity / Peiro, Ana / Sadee, Wolfgang / Salazar, Luis A. / Simmaco, Maurizio / Turpeinen, Miia / Schaik, Ron / Shin, Jae-Gook / Visvikis-Siest, Sophie / Zanger, Ulrich M.


CiteScore 2018: 1.01

SCImago Journal Rank (SJR) 2018: 0.277
Source Normalized Impact per Paper (SNIP) 2018: 0.446

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2363-8915
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Volume 33, Issue 4

Issues

Effects of CYP2C19*17 polymorphisms on the efficacy and safety of bromodigyrochlorophenylbenzodiazepine in patients with anxiety disorder and comorbid alcohol use disorder

Michael S. Zastrozhin
  • Department of Addictology, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
  • Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia
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/ Anastasiya P. AntonenkoORCID iD: http://orcid.org/0000-0002-6121-290X / Elena V. Nesterenko
  • Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia
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/ Leyla I. Seyfullaeva
  • Federal State Autonomous Educational Institution of Higher Education I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
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/ Violetta R. Mustafina
  • Federal State Autonomous Educational Institution of Higher Education I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russia
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/ Antonina P. Esakova
  • Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia
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/ Elena A. Grishina
  • Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
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/ Alexandr S. Sorokin
  • Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia
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/ Valentin Yu. Skryabin
  • Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia
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/ Ludmila M. Savchenko
  • Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
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/ Evgeny A. Bryun
  • Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia
  • Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
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/ Dmitry A. Sychev
  • Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
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Published Online: 2018-10-16 | DOI: https://doi.org/10.1515/dmpt-2018-0019

Abstract

Background

Bromodihydrochlorophenylbenzodiazepine (Phenazepam®) is used in the therapy of anxiety disorders in patients with alcohol dependence. However, Phenazepam therapy often turns out to be ineffective, and some patients develop dose-related adverse drug reactions (ADR): severe sedation, dizziness, headache, dyspepsia, falling, etc. That ensures the effectiveness of this category of patients. Despite the popularity of Phenazepam® as an anxiolytic drug, there is currently no accurate data on its biotransformation, as well as the effect of polymorphism of a gene on the efficacy and safety of bromodihydrochlorophenylbenzodiazepine in patients. The aim of our study was to study the effect of the polymorphism of the CYP2C19 gene on the efficacy and safety index of Phenazepam® for patients with anxiety disorders, using algorithms for optimizing the therapy of Phenazepam® to reduce the risk of pharmacological resistance and increase the effectiveness of therapy.

Methods

The study was conducted on 86 Russian patients suffering from alcohol dependence. Patients with trauma anxiety disorders received bromdihydrochlorphenylbenzodiazepine in tablets at a dose of 4.0 [2.0; 6.0] mg per day for 5 days. Genotyping was carried out by the method of polymer chain reaction in real time with allele-specific hybridization. Efficiency and safety assessment was carried out using psychometric scales and scales of Hospital Anxiety and Depression Scale (HADS) severity scores.

Results

Based on the results of the study, statistically significant differences in the number of scores on the scale of HADS severity of CYP2C19 CT on the third day of therapy were the following: (CC) 10.00 [9.00; 11.00], (CT) 14.00 [13.00; 16.00], (TT) 18.00 [17.00; 19.00], p=0.00, and also on the fifth day: (CC) 6.00 [5.00; 7.00], (CT) 17.50 [16.25; 19.75], (TT) 22.50 [20.00; 24.00], p=0.00. ADRs in patients with different genotypes for this polymorphic marker did not differ.

Conclusions

Thus, it has been shown that the polymorphism of the CYP2C19 gene may influence the effectiveness indices of Phenazepam therapy in patients with anxiety disorders comorbid with alcohol dependence. This should be taken into account in the appointment of this drug in this way in order to increase effectiveness of therapy and improve the quality of life.

Keywords: benzodiazepines; biotransformation; bromodihydrochlorobenzodiazepine; CYP2C19; personalized medicine; pharmacogenetics; Phenazepam

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About the article

Received: 2018-07-06

Accepted: 2018-09-10

Published Online: 2018-10-16

Published in Print: 2018-12-19


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

Research funding: This work was supported by the project titled “Fundamental research and exploratory research in priority areas of research” of the Russian Science Foundation and by the President’s Grant of state support for the young scientists (project № MK-2460.2018.7).

Employment or leadership: None declared.

Honorarium: None declared.

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


Citation Information: Drug Metabolism and Personalized Therapy, Volume 33, Issue 4, Pages 187–194, ISSN (Online) 2363-8915, ISSN (Print) 2363-8907, DOI: https://doi.org/10.1515/dmpt-2018-0019.

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