CYP3A Subfamily Activity Affects the Equilibrium Concentration of Phenazepam^® in Patients with Anxiety Disorders and Comorbid Alcohol use Disorder

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.

Keywords::

• alcohol addiction
• biotransformation
• bromdihydrochlorphenylbenzodiazepine
• CYP3A
• personalized medicine
• pharmacogenetics
• phenazepam

Financial & competing interests disclosure

The research was conducted with the financial support of grant from the President of the Russian Federation to assist young Russian scientists holding PhD degrees (project no. MK-2460.2018.7) and support of The Russian Science Foundation under project no. 16-15-00227: “conducting fundamental scientific research and exploratory research on priority thematic research areas”, “personalized antidepressant pharmacotherapy of patients with depressive disorders comorbid with alcohol use disorder based on pharmacogenetic, pharmacometabolomic and pharmacotranscriptomic biomarkers”. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The research was conducted with the financial support of grant from the President of the Russian Federation to assist young Russian scientists holding PhD degrees (project no. MK-2460.2018.7) and support of The Russian Science Foundation under project no. 16-15-00227: “conducting fundamental scientific research and exploratory research on priority thematic research areas”, “personalized antidepressant pharmacotherapy of patients with depressive disorders comorbid with alcohol use disorder based on pharmacogenetic, pharmacometabolomic and pharmacotranscriptomic biomarkers”. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.