CYP3A subfamily activity affects the equilibrium concentration of Phenazepam® in patients with anxiety disorders and comorbid alcohol use disorder-Reference-Cited by-同舟云学术

CYP3A subfamily activity affects the equilibrium concentration of Phenazepam® in patients with anxiety disorders and comorbid alcohol use disorder

Published:2020-05 Issue:7 Volume:21 Page:449-457
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Zastrozhin Mikhail Sergeevich¹²^ORCID,Skryabin Valentin Yurievich¹,Sorokin Alexander Sergeevich¹,Petukhov Aleksey Evgenievich¹,Smirnov Valery Valerievich³⁴,Pankratenko Ekaterina Petrovna¹,Grishina Elena Anatolievna²,Ryzhikova Kristina Anatolievna²,Panov Aleksey Sergeevich²,Savchenko Ludmila Mikhailovna²,Bryun Evgeny Alekseevich¹²,Sychev Dmitry Alekseevich²

Affiliation:

1. Laboratory of Genetics & Genomics, Moscow Research & Practical Centre on Addictions of The Moscow Department of Healthcare, Moscow, 109390, Russian Federation

2. Department of Addictology, Russian Medical Academy of Continuous Professional Education of The Ministry of Health of The Russian Federation, Moscow, 123995, Russian Federation

3. Laboratory of Clinical Pharmacology, National Research Centre – Institute of Immunology of The Federal Biomedical Agency of The Russian Federation, Moscow, 115478, Russian Federation

4. Department of Pharmaceutical and Toxicological Chemistry A.P. Arzamastseva, I.M. Sechenov First Moscow State Medical University of The Ministry of Health of The Russian Federation (Sechenov University), Moscow, 119991, Russia

Abstract

Phenazepam® is prescribed to relieve anxiety and sleep disorders during alcohol withdrawal, although it is associated with undesirable side effects. Aim: To demonstrate changes in the safety and efficacy profiles of Phenazepam in patients with anxiety disorders and comorbid alcohol use disorder. Materials & methods: A total of 94 Russian patients with alcohol use disorder received 4.0 mg of Phenazepam per day in tablets. We used a urinary 6-beta-hydroxycortisol/cortisol ratio to evaluate CYP3A activity. Results: A statistically significant inverse correlation between Phenazepam plasma concentration and CYP3A activity was found (r = -0.340 and p = 0.017). Correlation between the concentration/dose ratio and phenotyping results was also statistically significant (r = 0.301 and p = 0.026). Conclusion: The safety and efficacy of Phenazepam depend on CYP3A genetic polymorphisms.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs-2019-0071

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