The relationship between the CYP2C19*17 genetic polymorphism and the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome

Abstract

The aim of our study was to study the relationship between the CYP2C19 genetic polymorphism and the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome in order to develop algorithms for optimizing the therapy of diazepam to reduce the risk of dose-dependent adverse drug reactions and pharmacoresistance.Materials and methods. The study was conducted on 30 Russian male patients suffering from alcohol withdrawal syndrome. For the treatment of anxiety, fear and emotional tension, patients received diazepam in injections at a dosage of 30,0 mg / day for 5 days. Genotyping was performed by real-time polymerase chain reaction with allele-specific hybridization. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions: the Clinical Institute Withdrawal Assessment for Alcohol scale, the visual-analogue scale of the craving for alcohol, and the side-effect scale.Results. Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 -806C>T genotypes: (CC) –12,0 [–15,0; –8,0], (CT + TT) –7.0 [–14,0; –5,0], p = 0,001. The scores on the UKU scale, which was used to evaluate the safety of therapy, were also different: (CC) 8,0 [6,0; 12,0], (CT + TT) 6,0 [6,0; 12,0], p = 0,006.Conclusion. The relationships between the CYP2C19 genetic polymorphism and the efficacy and safety of diazepam were demonstrated. This should be taken into consideration when prescribing this drug to such patients in order to reduce the risk of adverse drug reactions and pharmacoresistance.

Relations of CYP2C19*2 genetic polymorphisms to plasma and saliva concentrations of diazepam in patients hospitalized for alcohol withdrawal

“…These results are consistent with the findings of our previous study focused on investigation of the CYP2C19*2 genetic polymorphism, which had a 2-times lower sample size and enrolled 50 patients [7]. Furthermore, previous studies which were conducted by our research group [14,15], confirm the importance, relevance and possibility to investigate the personalized approach to the prescription of BZDs (and specifically diazepam) in such cohort of patients.…”

“…Diazepam is mainly metabolized via CYP2C19 and CYP3A4 to its major active metabolite, desmethyldiazepam. Recent studies revealed the effect of CYP2C19 and CYP3A4 genetic polymorphisms on the pharmacokinetics of BZDs [7][8][9][10]. The differences in the activity of these enzymes are genetically determined.…”