ppanPersonalized Psychiatry and NeurologyPersonalized Psychiatry and Neurology2712-9179V. M. Bekhterev National Medical Research Centre for Psychiatry and Neurology of the Ministry of Health of the Russian Federation (Bekhterev NMRC PN)10.52667/2712-9179-2021-1-1-84-92ppan-14Research ArticleARTICLERelations of CYP2C19*2 genetic polymorphisms to plasma and saliva concentrations of diazepam in patients hospitalized for alcohol withdrawalSkryabinV. Yu.sardonios@yandex.ruZastrozhinM. S.GrishinaE. A.RyzhikovaK. A.ShipitsynV. V.GalaktionovaT. E.BryunE. A.SychevD. A.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 FederationRussian FederationRussian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian FederationRussian FederationMoscow Research and Practical Centre on Addictions of the Moscow Department of HealthcareRussian Federation202118052021118492Copyright © Skryabin V.Y., Zastrozhin M.S., Grishina E.A., Ryzhikova K.A., Shipitsyn V.V., Galaktionova T.E., Bryun E.A., Sychev D.A., 20212021Skryabin V.Y., Zastrozhin M.S., Grishina E.A., Ryzhikova K.A., Shipitsyn V.V., Galaktionova T.E., Bryun E.A., Sychev D.A.Skryabin V.Y., Zastrozhin M.S., Grishina E.A., Ryzhikova K.A., Shipitsyn V.V., Galaktionova T.E., Bryun E.A., Sychev D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.jppn.ru/jour/article/view/14

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).

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The authors declare that there are no conflicts of interest present.