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Relations of CYP2C19*2 genetic polymorphisms to plasma and saliva concentrations of diazepam in patients hospitalized for alcohol withdrawal

https://doi.org/10.52667/2712-9179-2021-1-1-84-92

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Abstract

Diazepam is one of the most widely prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS). However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions. Previous studies have shown that the metabolism of diazepam involves the CYP2C19 isoenzyme, whose activity is highly dependent on polymorphism of the encoding gene. The objective of our study was to investigate the effects of CYP2C19*2 genetic polymorphisms on plasma and saliva concentrations of diazepam as well as its impact on the efficacy and safety rates of therapy in patients with AWS. The study was conducted on 100 Russian male patients with AWS who received diazepam in injections at a dosage of 30.0 mg/day for 5 days. Genotyping was performed by real-time polymerase chain reaction. The efficacy and safety assessment was performed using psychometric scales. We revealed differences in the efficacy and safety of therapy in patients with different CYP2C19 681G>A genotypes. Therapeutic drug monitoring (TDM) revealed the statistically significant differences in the levels of diazepam plasma concentration: (GG) 199.83 [82.92; 250.58] vs (GA+AA) 313.47 [288.99; 468.33], p=0.040, and diazepam saliva concentration: (GG) 2.80 [0.73; 3.80] vs (GA+AA) 5.33 [5.14; 6.00], p=0.003).

About the Authors

V. Yu. Skryabin
Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation
Russian Federation


M. S. Zastrozhin
Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation
Russian Federation


E. A. Grishina
Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation
Russian Federation


K. A. Ryzhikova
Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation
Russian Federation


V. V. Shipitsyn
Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare
Russian Federation


T. E. Galaktionova
Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation
Russian Federation


E. A. Bryun
Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation
Russian Federation


D. A. Sychev
Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation
Russian Federation


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For citation:


Skryabin V.Y., Zastrozhin M.S., Grishina E.A., Ryzhikova K.A., Shipitsyn V.V., Galaktionova T.E., Bryun E.A., Sychev D.A. Relations of CYP2C19*2 genetic polymorphisms to plasma and saliva concentrations of diazepam in patients hospitalized for alcohol withdrawal. Personalized Psychiatry and Neurology. 2021;1(1):84-92. https://doi.org/10.52667/2712-9179-2021-1-1-84-92

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