Skryabin Valentin Yurievich, Zastrozhin Mikhail, Torrado Marco, Grishina Elena, Ryzhikova Kristina, Shipitsyn Valery, Galaktionova Tatiana, Sorokin Alexander, Bryun Evgeny, Sychev Dmitry
Moscow Department of Healthcare, Moscow, Russia.
Ministry of Health of the Russian Federation, Moscow, Russia.
Hosp Pharm. 2021 Oct;56(5):592-596. doi: 10.1177/0018578720931756. Epub 2020 Jun 2.
Diazepam is one of the most widely prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS), which includes the symptoms of anxiety, fear, and emotional tension. However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions, reducing the efficacy of therapy. The purpose of our study was to investigate the effects of CYP2C19*17 genetic polymorphisms on the steady-state concentration of diazepam in patients with AWS. The study was conducted on 50 Russian male patients suffering from the AWS. For the therapy of psychomotor agitation, 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. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Therapeutic drug monitoring (TDM) was performed using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 - genotypes: (*1/*1) -12.0 [-15.0; -8.0], (*1/*17+*17/*17) -7.0 [-14.0; -5.0], < .001, as well as the results of TDM: () 250.70 [213.34; 308.53] ng/mL (*1/*17+*17/17) 89.12 [53.26; 178.07] ng/mL, < .001. Thus, our study enrolling 50 patients with AWS, showed the effects of CYP2C1917 genetic polymorphisms on the efficacy and safety rates of diazepam. Furthermore, we revealed the statistically significant difference in the levels of plasma steady-state concentrations of diazepam in patients carrying different genotypes.
地西泮是治疗酒精戒断综合征（AWS）最常用的镇静剂之一，该综合征包括焦虑、恐惧和情绪紧张等症状。然而，地西泮治疗往往无效，一些患者会出现剂量依赖性药物不良反应，降低了治疗效果。我们研究的目的是调查CYP2C19*17基因多态性对AWS患者地西泮稳态浓度的影响。该研究对50名患有AWS的俄罗斯男性患者进行。为了治疗精神运动性激越、焦虑、恐惧和情绪紧张，患者接受地西泮注射治疗，剂量为30.0毫克/天，持续5天。通过实时聚合酶链反应进行基因分型。使用心理测量量表和药物不良反应严重程度评估量表进行疗效和安全性评估。采用高效液相色谱-质谱联用（HPLC-MS/MS）法进行治疗药物监测（TDM）。根据研究结果，我们发现不同CYP2C19基因型患者的治疗效果存在差异：（*1/*1）-12.0 [-15.0；-8.0]，（*1/*17+*17/*17）-7.0 [-14.0；-5.0]，P<0.001，以及TDM结果：（*1/*1）250.70 [213.34；308.53]纳克/毫升，（*1/*17+*17/17）89.12 [53.26；178.07]纳克/毫升，P<0.001。因此，我们纳入50名AWS患者的研究显示了CYP2C1917基因多态性对地西泮疗效和安全率的影响。此外，我们发现携带不同基因型患者的地西泮血浆稳态浓度水平存在统计学显著差异。
