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

Phenazepam is prescribed to relieve anxiety and sleep disorders during alcohol withdrawal, although it is associated with undesirable side effects. To demonstrate changes in the safety and efficacy profiles of Phenazepam in patients with anxiety disorders and comorbid alcohol use disorder. A total o...

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Bibliographic Details
Published in:Pharmacogenomics 2020-05, Vol.21 (7), p.449-457
Main Authors: Zastrozhin, Mikhail Sergeevich, Skryabin, Valentin Yurievich, Sorokin, Alexander Sergeevich, Petukhov, Aleksey Evgenievich, Smirnov, Valery Valerievich, Pankratenko, Ekaterina Petrovna, Grishina, Elena Anatolievna, Ryzhikova, Kristina Anatolievna, Panov, Aleksey Sergeevich, Savchenko, Ludmila Mikhailovna, Bryun, Evgeny Alekseevich, Sychev, Dmitry Alekseevich
Format: Article
Language:English
Subjects:
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
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Summary:Phenazepam is prescribed to relieve anxiety and sleep disorders during alcohol withdrawal, although it is associated with undesirable side effects. To demonstrate changes in the safety and efficacy profiles of Phenazepam in patients with anxiety disorders and comorbid alcohol use disorder. 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. 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). The safety and efficacy of Phenazepam depend on CYP3A genetic polymorphisms.
ISSN:1462-2416
1744-8042
DOI:10.2217/pgs-2019-0071