How do CYP2C19*2 and CYP2C19*17 genetic polymorphisms affect the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome?

Valentin Yu Skryabinhttp://orcid.org/https://orcid.org/0000-0002-4942-8556 1 , Mikhail S. Zastrozhin 2 , 3 , Marco V. Torrado 4 , Elena A. Grishina 3 , Kristina A. Ryzhikova 3 , Valery V. Shipitsyn 2 , Tatiana E. Galaktionova 2 , Alexander S. Sorokin 2 , Evgeny A. Bryun 2 , 3 ,  and Dmitry A. Sychev 3
  • 1 Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, 37/1 Lyublinskaya Street, Moscow, Russia
  • 2 Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia
  • 3 Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
  • 4 University of Lisbon, Faculty of Medicine, ISAMB (Instituto de Saúde Ambiental), Avenida Professor Egas Moniz MB, Lisboa, Portugal
Valentin Yu SkryabinORCID iD: https://orcid.org/0000-0002-4942-8556, Mikhail S. Zastrozhin
  • 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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, Marco V. Torrado
  • University of Lisbon, Faculty of Medicine, ISAMB (Instituto de Saúde Ambiental), Avenida Professor Egas Moniz MB, Lisboa, Portugal
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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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, Kristina A. Ryzhikova
  • Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
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, Valery V. Shipitsyn
  • Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia
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, Tatiana E. Galaktionova
  • Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia
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, Alexander S. Sorokin
  • Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia
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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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and 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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Abstract

Background

Diazepam is one of the most commonly prescribed tranquilizers for therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on its efficacy and safety. The objective of our study was to investigate the effect of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy and safety of diazepam in patients with AWS.

Methods

The study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg/day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions.

Results

Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 681G>A (CYP2C19*2, rs4244285) genotypes: (CYP2C19*1/*1) −8.5 [−15.0; −5.0], (CYP2C19*1/*2 and CYP2C19*2/*2) −12.0 [−13.0; −9.0], p = 0.021. The UKU scale scores, which were used to evaluate the safety of therapy, were also different: (CYP2C19*1/*1) 7.0 [6.0; 12.0], (CYP2C19*1/*2 and CYP2C19*2/*2) 9.5 [8.0; 11.0], p = 0.009. Patients carrying different CYP2C19 –806C>T (CYP2C19*17, rs12248560) genotypes also demonstrated differences in therapy efficacy and safety rates.

Conclusions

Thus, the effects of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy of diazepam were demonstrated.

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Drug Metabolism and Personalized Therapy (DMPT ) publishes the results of research and review articles in the fields of clinical and biological pharmacology, drug metabolizing enzymes, pharmacogenetics/pharmacogenomics, pharmacokinetics and drug-drug interactions. DMPT is the official journal of the European Society of Pharmacogenomics and Personalised Therapy.

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