Hostname: page-component-54dcc4c588-42vt5 Total loading time: 0 Render date: 2025-10-11T18:49:27.271Z Has data issue: false hasContentIssue false
  • English
  • Français

Effect of CYP2C19*17 gene polymorphism on plasma levels of diazepam and nordiazepam in Turkish patients with Alcohol Withdrawal Syndrome

Published online by Cambridge University Press:  26 August 2025

S. Özkan-Kotiloğlu ,
D. Kaya-Akyüzlü ,
M. A. Yıldırım ,
M. Danışman ,
C. Bozmaoğlu ,
K. C. Tok ,
M. Gümüştaş ,
I. Özgür-İlhan  and
S. Süzen
S. Özkan-Kotiloğlu*
Affiliation:
Molecular Biology and Genetics, Kırşehir Ahi Evran University, Kırşehir Institute of Forensic Sciences, Ankara University
D. Kaya-Akyüzlü
Affiliation:
Institute of Forensic Sciences, Ankara University
M. A. Yıldırım
Affiliation:
Institute of Forensic Sciences, Ankara University
M. Danışman
Affiliation:
AMATEM Clinic, Ankara Training and Research Hospital
C. Bozmaoğlu
Affiliation:
Institute of Forensic Sciences, Ankara University
K. C. Tok
Affiliation:
Institute of Forensic Sciences, Ankara University
M. Gümüştaş
Affiliation:
Institute of Forensic Sciences, Ankara University
I. Özgür-İlhan
Affiliation:
Department of Mental Health and Diseases
S. Süzen
Affiliation:
Department of Pharmaceutical Toxicology, Ankara University, Ankara, Türkiye
*
*Corresponding author.

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Introduction

Alcohol withdrawal syndrome (AWS) is not a common medical condition in general population however it affects patients with alcohol use disorder (AUD) and causes severe complications when diagnosed late or left untreated. Diazepam is a benzodiazepine, which is used to treat various diseases such as insomnia, anxiety, muscle spasm, pain and AWS. Compared to other benzodiazepines, diazepam is more efficient to prevent delirium and decrease withdrawal due to its long half-life. Diazepam is metabolised to its main metabolite nordiazepam with the enzymes expressed by CYP2C19 and CYP3A4 genes. It has been reported that metabolic activity of the enzymes encoded by CYP2C19 gene may be varied due to genetic polymorphisms leading a change in the efficiency of treatment via effecting the plasma level of drugs metabolised by CYP2C19.

Objectives

The aim of this study is to investigate whether CYP2C19*17 gene polymorphism has an impact on plasma levels of diazepam and nordiazepam in the Turkish patients with AWS and under oral diazepam treatment.

Methods

The study included 50 male patients who were in withdrawal state and taking diazepam therapy. CYP2C19*17 polymorphism was determined by PCR-RFLP method. Plasma levels of diazepam (DZP) and nordiazepam (NDZP) were detected by HPLC.

Results

Genotype frequencies were calculated as 66% for CC, 30% for CT and 4% for TT. Dose-normalized DZP and dose-normalized NDZP values were 0.049 μg/ml per mg/day and 0,056 μg/ml per mg/day, respectively. No statistical significance was observed in the levels of normalized DZP and NDZP when CC and CT+TT genotypes were compared (p= 0.073 and p=0.282, respectively).

Conclusions

The effect of CYP2C19*17 polymorphism on the plasma levels of DZP and NDZP following long term oral diazepam to treat patients with AWS was determined for the first time. With the help of current study, first data on Turkish population was obtained and may be useful for personalized therapy in the future.

This study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) under the Grant Number 121C441. The authors thank to TUBITAK for their supports.

Disclosure of Interest

None Declared

Information

Type
Abstract
Information
European Psychiatry , Volume 68 , Special Issue S1: Abstracts of the 33rd European Congress of Psychiatry , April 2025 , pp. S292
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of European Psychiatric Association
Submit a response

Comments

No Comments have been published for this article.