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

Pharmacogenomics. 2020 May;21(7):449-457. doi: 10.2217/pgs-2019-0071. Epub 2020 Apr 27.

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: CYP3A; alcohol addiction; biotransformation; bromdihydrochlorphenylbenzodiazepine; personalized medicine; pharmacogenetics; phenazepam.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcoholism / drug therapy*
  • Alcoholism / enzymology*
  • Alcoholism / epidemiology
  • Alcoholism / genetics
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / enzymology*
  • Anxiety Disorders / epidemiology
  • Anxiety Disorders / genetics
  • Benzodiazepines / pharmacology
  • Benzodiazepines / therapeutic use*
  • Comorbidity
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism*
  • Enzyme Activation / physiology
  • Female
  • GABA Agents / pharmacology
  • GABA Agents / therapeutic use
  • Humans
  • Male
  • Russia / epidemiology

Substances

  • GABA Agents
  • Benzodiazepines
  • phenazepam
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A