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

Michael Sergeevich ZastrozhinValentin Yurievich SkryabinAlexander Sergeevich SorokinAleksey Evgenievich PetukhovValery Valerievich SmirnovEkaterina Petrovna PankratenkoElena Anatolievna GrishinaKristina Anatolievna RyzhikovaAleksey Sergeevich PanovLudmila Mikhailovna SavchenkoEvgeny Alekseevich BryunDmitry Alekseevich Sychev
Published in: Pharmacogenomics (2020)
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.
Keyphrases
  • alcohol use disorder
  • sleep quality
  • physical activity
  • high throughput
  • molecular dynamics simulations
  • transcription factor