Effects of CYP2C19*2 polymorphisms on the efficacy and safety of phenazepam in patients with anxiety disorder and comorbid alcohol use disorder

Pharmacogenomics. 2020 Jan;21(2):111-123. doi: 10.2217/pgs-2019-0019.

Abstract

Introduction: Phenazepam therapy can often be ineffective and some patients develop dose-related adverse drug reactions. Aim. The purpose of this research was to study the effect of the CYP2C19*2 (681G>A, rs4244285) in patients with anxiety disorders and alcohol dependence taking phenazepam therapy. Materials & methods: Patients (175 males, average age: 37.16 ± 7.84 years) received phenazepam in tablet form for 5 days. Genotyping was performed by real-time polymerase chain reaction. Results: The statistically significant differences in the UKU Side-Effect Rating Scale scores on the fifth day of therapy: (CYP2C19*1/*1) 2.00 [1.00; 2.00), (CYP2C19*1/*2) 7.00 (7.00; 7.00), (CYP2C19*2/*2) 9.00 (8.00; 9.00), p < 0.001. Conclusion: This study demonstrated the different efficacy and safety of phenazepam in patients with different genotypes of CYP2C19*2.

Keywords: CYP2C19; alcohol addiction; anxiety disorders; benzodiazepines; biotransformation; bromodihydrochlorobenzodiazepine; personalized medicine; phenazepam.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcoholism / genetics*
  • Alcoholism / pathology
  • Anti-Anxiety Agents / administration & dosage
  • Anti-Anxiety Agents / adverse effects
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / genetics
  • Anxiety Disorders / pathology
  • Benzodiazepines / administration & dosage*
  • Benzodiazepines / adverse effects
  • Cytochrome P-450 CYP2C19 / genetics*
  • Female
  • Genotype
  • Humans
  • Male

Substances

  • Anti-Anxiety Agents
  • Benzodiazepines
  • phenazepam
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19