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Effects of CYP2C19*17 polymorphisms on the efficacy and safety of bromodigyrochlorophenylbenzodiazepine in patients with anxiety disorder and comorbid alcohol use disorder.
Drug Metab Pers Ther 2018; 33(4):187-194DM

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.

Authors+Show Affiliations

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.Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, 37/1 Lyublinskaya Street, Moscow 109390, Russia.Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia.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.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.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.Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia.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.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.Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30325732

Citation

Zastrozhin, Michael S., et al. "Effects of CYP2C19*17 Polymorphisms On the Efficacy and Safety of Bromodigyrochlorophenylbenzodiazepine in Patients With Anxiety Disorder and Comorbid Alcohol Use Disorder." Drug Metabolism and Personalized Therapy, vol. 33, no. 4, 2018, pp. 187-194.
Zastrozhin MS, Antonenko AP, Nesterenko EV, et al. Effects of CYP2C19*17 polymorphisms on the efficacy and safety of bromodigyrochlorophenylbenzodiazepine in patients with anxiety disorder and comorbid alcohol use disorder. Drug Metab Pers Ther. 2018;33(4):187-194.
Zastrozhin, M. S., Antonenko, A. P., Nesterenko, E. V., Seyfullaeva, L. I., Mustafina, V. R., Esakova, A. P., ... Sychev, D. A. (2018). Effects of CYP2C19*17 polymorphisms on the efficacy and safety of bromodigyrochlorophenylbenzodiazepine in patients with anxiety disorder and comorbid alcohol use disorder. Drug Metabolism and Personalized Therapy, 33(4), pp. 187-194. doi:10.1515/dmpt-2018-0019.
Zastrozhin MS, et al. Effects of CYP2C19*17 Polymorphisms On the Efficacy and Safety of Bromodigyrochlorophenylbenzodiazepine in Patients With Anxiety Disorder and Comorbid Alcohol Use Disorder. Drug Metab Pers Ther. 2018 12 19;33(4):187-194. PubMed PMID: 30325732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of CYP2C19*17 polymorphisms on the efficacy and safety of bromodigyrochlorophenylbenzodiazepine in patients with anxiety disorder and comorbid alcohol use disorder. AU - Zastrozhin,Michael S, AU - Antonenko,Anastasiya P, AU - Nesterenko,Elena V, AU - Seyfullaeva,Leyla I, AU - Mustafina,Violetta R, AU - Esakova,Antonina P, AU - Grishina,Elena A, AU - Sorokin,Alexandr S, AU - Skryabin,Valentin Yu, AU - Savchenko,Ludmila M, AU - Bryun,Evgeny A, AU - Sychev,Dmitry A, PY - 2018/07/06/received PY - 2018/09/10/accepted PY - 2018/10/17/pubmed PY - 2019/6/18/medline PY - 2018/10/17/entrez KW - CYP2C19 KW - Phenazepam KW - benzodiazepines KW - biotransformation KW - bromodihydrochlorobenzodiazepine KW - personalized medicine KW - pharmacogenetics SP - 187 EP - 194 JF - Drug metabolism and personalized therapy JO - Drug Metab Pers Ther VL - 33 IS - 4 N2 - 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. SN - 2363-8915 UR - https://www.unboundmedicine.com/medline/citation/30325732/Effects_of_CYP2C19*17_polymorphisms_on_the_efficacy_and_safety_of_bromodigyrochlorophenylbenzodiazepine_in_patients_with_anxiety_disorder_and_comorbid_alcohol_use_disorder L2 - https://www.degruyter.com/doi/10.1515/dmpt-2018-0019 DB - PRIME DP - Unbound Medicine ER -