Skryabin Valentin Yurievich, Zastrozhin Mikhail Sergeevich, Parkhomenko Aleksandra Aleksandrovna, Pankratenko Ekaterina Petrovna, Pozdnyakov Sergei Aleksandrovich, Denisenko Natalia Pavlovna, Akmalova Kristina Anatolyevna, Bryun Evgeny Alekseevich, Sychev Dmitry Alekseevich
Moscow Research and Practical Centre on Addictions of the Moscow, Department of Healthcare, Moscow, Russia.
Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia.
Hosp Pharm. 2023 Aug;58(4):363-367. doi: 10.1177/00185787231155842. Epub 2023 Feb 22.
Haloperidol is commonly prescribed to patients with alcohol-induced psychotic disorder (AIPD). Notably however, individuals differ extensively with regards to therapeutic response and adverse drug reactions (ADRs). Previous studies have shown that haloperidol biotransformation is mainly metabolized by CYP2D6. The objective of our study was to investigate the use of pharmacogenetic (CYP2D64 genetic polymorphism) and pharmacometabolomic biomarkers to predict haloperidol efficacy and safety rates. The study enrolled 150 patients with AIPD. Therapy included haloperidol in a daily dose of 5 to 10 mg/day by injections for 5 days. Efficacy and safety of treatment were evaluated using the validated psychometric scales PANSS, UKU, and SAS. No association of the urinary 6-НО-ТНВС/pinoline ratio values which could be evidence of the CYP2D6 activity level with both the efficacy and safety rates of haloperidol was demonstrated. However, a statistically significant association between haloperidol safety profile and CYP2D64 genetic polymorphism was demonstrated ( < .001). To predict haloperidol efficacy and safety rates, utilization of pharmacogenetic testing that defines CYP2D6*4 genetic polymorphism is found preferable over the use of the pharmacometabolomic marker in a clinical setting.
氟哌啶醇常用于治疗酒精所致精神障碍（AIPD）患者。然而，值得注意的是，个体在治疗反应和药物不良反应（ADR）方面存在很大差异。先前的研究表明，氟哌啶醇的生物转化主要通过CYP2D6代谢。我们研究的目的是调查利用药物遗传学（CYP2D64基因多态性）和药物代谢组学生物标志物来预测氟哌啶醇的疗效和安全率。该研究纳入了150例AIPD患者。治疗方法为每日注射5至10毫克/天的氟哌啶醇，共5天。使用经过验证的心理测量量表PANSS、UKU和SAS评估治疗的疗效和安全性。未发现可作为CYP2D6活性水平证据的尿6-OH-TBAS/匹诺啉比值与氟哌啶醇的疗效和安全率之间存在关联。然而，氟哌啶醇安全性与CYP2D64基因多态性之间存在统计学上的显著关联（P<0.001）。为了预测氟哌啶醇的疗效和安全率，在临床环境中，利用确定CYP2D6*4基因多态性的药物遗传学检测比使用药物代谢组学标志物更可取。
