基因 > 多态性与急性酒精性幻觉症患者的氟哌啶醇平衡浓度水平的关系。

Relationship of the > Polymorphism of the Gene to the Equilibrium Concentration Levels of Haloperidol in Patients with Acute Alcoholic Hallucinosis.

机构信息

Parkhomenko, postgraduate student at the Department of Addiction Medicine, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia.

Zastrozhin, PhD, MD, Associate professor of addiction psychiatry department.

出版信息

Psychopharmacol Bull. 2023 Dec 4;53(4):15-22.

PMID:38076663

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10698856/

Abstract

UNLABELLED

Haloperidol is currently used in addictology for the treatment of acute psychotic disorders, including acute alcoholic hallucinosis. The use of haloperidol is often accompanied by the occurrence of adverse drug reactions (ADRs). There is evidence that CYP2D6 isoenzyme is involved in the biotransformation of haloperidol.

AIM

The study aimed to evaluate the relationship of 1846G > A polymorphism of the CYP2D6 gene to the equilibrium concentration levels of haloperidol in patients with acute alcoholic hallucinosis.

MATERIAL AND METHODS

The study was conducted on 100 male patients with acute alcoholic hallucinosis (mean age 41.4 ± 14.4 years). The efficacy profile was evaluated using the PANSS (Positive and Negative Syndrome Scale) scale. The safety of therapy was assessed using the UKU Side-Effect Rating Scale and the SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scale. Genotyping was performed using the real-time polymerase chain reaction (Real-time PCR). Equilibrium plasma concentration levels of haloperidol were investigated using the high-performance liquid chromatography with mass spectrometry (HPLC with MS/MS).

RESULTS

No statistically significant results were obtained during the therapy efficacy assessment (dynamics of the PANSS score: genotype (-13.00 [-16.00; -16.00; -11.00]), genotype (-15.00 [-16.75; -13.00], p = 0.728). There was a statistically significant difference in safety assessment scores (dynamics of the UKU score: genotype (8.00 [7.00; 10.00]), genotype (15.00 [9.25; 18.00], p < 0.001); dynamics of the SAS score: genotype (11.00 [9.00; 14.00]), genotype (14.50 [12.00; 18.00], p < 0.001). The pharmacokinetic study results showed a statistically significant difference: (3.13 [2.32; 3.95]), (3.89 [2.92; 5.26], p = 0.010). Thus, a study conducted on a group of 100 patients with acute alcoholic hallucinosis demonstrated an association between the > polymorphism of the gene () and the safety profile of haloperidol therapy. We also revealed the presence of statistically significant difference in the equilibrium concentration levels of haloperidol in patients with the and genotypes.

CONCLUSION

It can be concluded that patients with the genotype have a higher risk of ADRs compared to patients carrying the genotype. It is shown that > polymorphism of the gene () has a statistically significant effect on the equilibrium concentration levels of haloperidol.

摘要

目的

评估 CYP2D6 基因 1846G＞A 多态性与急性酒精性幻觉患者体内氟哌啶醇平衡浓度的关系。

材料与方法

本研究纳入 100 例男性急性酒精性幻觉患者（平均年龄 41.4±14.4 岁）。采用阳性与阴性综合征量表（PANSS）评估疗效。采用 UKU 副作用评定量表和 Simpson-Angus 量表（用于评估锥体外系症状）评估治疗安全性。采用实时聚合酶链反应（Real-time PCR）进行基因分型。采用高效液相色谱-质谱联用（HPLC-MS/MS）检测氟哌啶醇的平衡血浆浓度。

结果

在治疗效果评估期间未获得具有统计学意义的结果（PANSS 评分动态：基因型（-13.00 [-16.00；-16.00；-11.00]），基因型（-15.00 [-16.75；-13.00]），p=0.728）。在安全性评估评分方面存在统计学差异（UKU 评分动态：基因型（8.00 [7.00；10.00]），基因型（15.00 [9.25；18.00]），p＜0.001；Simpson-Angus 评分动态：基因型（11.00 [9.00；14.00]），基因型（14.50 [12.00；18.00]），p＜0.001）。药代动力学研究结果显示存在统计学差异：（3.13 [2.32；3.95]），（3.89 [2.92；5.26]），p=0.010）。因此，对 100 例急性酒精性幻觉患者进行的研究表明，基因（）多态性与氟哌啶醇治疗的安全性特征相关。此外，我们还发现基因型和基因型患者的氟哌啶醇平衡浓度水平存在统计学差异。