RESUMEN
BACKGROUND: Diazepam is one of the most commonly prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on the efficacy and safety of diazepam therapy. OBJECTIVE: The objective of our study was to study the effect of CYP3A isoenzymes activity on the efficacy and safety of diazepam in patients with AWS. METHODS: The study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg / day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. RESULTS: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP3A4 C>T intron 6 (rs35599367) genotypes: (CC) -9.0 [-13.0; -5.0], (CT+TT) -13.5 [-15.0; -10.0], p = 0.014. The scores on the UKU scale, which was used to evaluate the safety of therapy, were also different: (CC) 7.5 [6.0; 11.0], (CT+TT) 11.0 [8.0; 12.0], p = 0.003. CONCLUSION: Possible relationship between the CYP3A activity, evaluated by the content of the urinary endogenous substrate of the given isoenzyme and its metabolite, the 6-beta-hydroxy cortisol (6-ß-HC) / cortisol ratio, and the efficacy of diazepam was demonstrated. This possible relationship was also supported by the genotyping results. This should be taken into consideration when prescribing this drug to such patients in order to reduce the risk of pharmacoresistance.
Asunto(s)
Alcoholismo , Citocromo P-450 CYP3A , Diazepam , Hipnóticos y Sedantes , Síndrome de Abstinencia a Sustancias , Alcoholismo/complicaciones , Alcoholismo/tratamiento farmacológico , Alcoholismo/genética , Citocromo P-450 CYP3A/genética , Diazepam/efectos adversos , Diazepam/uso terapéutico , Humanos , Hidrocortisona/uso terapéutico , Hipnóticos y Sedantes/efectos adversos , Hipnóticos y Sedantes/uso terapéutico , Masculino , Polimorfismo Genético , Síndrome de Abstinencia a Sustancias/diagnóstico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/etiología , Síndrome de Abstinencia a Sustancias/genéticaRESUMEN
Background Diazepam is one of the most commonly prescribed tranquilizers for therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on its efficacy and safety. The objective of our study was to investigate the effect of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy and safety of diazepam in patients with AWS. Methods The study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg/day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Results Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 681G>A (CYP2C19*2, rs4244285) genotypes: (CYP2C19*1/*1) -8.5 [-15.0; -5.0], (CYP2C19*1/*2 and CYP2C19*2/*2) -12.0 [-13.0; -9.0], p = 0.021. The UKU scale scores, which were used to evaluate the safety of therapy, were also different: (CYP2C19*1/*1) 7.0 [6.0; 12.0], (CYP2C19*1/*2 and CYP2C19*2/*2) 9.5 [8.0; 11.0], p = 0.009. Patients carrying different CYP2C19 -806C>T (CYP2C19*17, rs12248560) genotypes also demonstrated differences in therapy efficacy and safety rates. Conclusions Thus, the effects of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy of diazepam were demonstrated.
Asunto(s)
Citocromo P-450 CYP2C19/genética , Diazepam/efectos adversos , Polimorfismo Genético/genética , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Citocromo P-450 CYP2C19/sangre , Diazepam/administración & dosificación , Diazepam/sangre , Relación Dosis-Respuesta a Droga , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Abstinencia a Sustancias/genéticaRESUMEN
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.