Zastrozhin Mikhail Sergeevich, Grishina Elena Anatolievna, Ryzhikova Kristina Anatolievna, Smirnov Valery Valerievich, Savchenko Ludmila Mikhailovna, Bryun Evgeny Alekseevich, Sychev Dmitry Alekseevich
Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russian Federation.
Moscow Research and Practical Centre on Addictions, Moscow Department of Healthcare.
Pharmgenomics Pers Med. 2017 Dec 28;11:1-5. doi: 10.2147/PGPM.S144503. eCollection 2018.
Isoenzymes CYP2D6 and CYP3A4, the activity of which varies widely, are involved in metabolism of haloperidol and may influence its profile of efficacy and safety.
The primary aim of this study was to estimate the relationship between CYP3A5 gene polymorphism, activity of the CYP3A isoenzyme, and the risk of development of adverse drug reactions by haloperidol in patients with alcohol abuse.
Sixty-six male alcohol-addicted patients participated in the study. The safety of haloperidol was evaluated by Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU) and Simpson-Angus Scale for extrapyramidal symptoms (SAS). The activity of CYP3A was evaluated by determining the concentrations of an endogenous substrate of this isoenzyme (cortisol) and its urinary metabolite (6-beta-hydroxycortisol, 6-B-HC). Genotyping of CYP3A5*3 was performed by real-time polymerase chain reaction with allele-specific hybridization.
The frequency of A-allele occurrence in Russian population was very poor (2.27%). CYP3A53 polymorphism had no influence on safety profile indicators of haloperidol (UKU scale: =0.55, SAS scale: =0.64). In addition, there was no statistical significant difference between the values of indexes of the metabolic ratio (6-B-HC/cortisol) in groups with different genotypes of CYP3A53: GG 5.00 (3.36; 6.39) vs AG 5.26 (2.10; 6.78) (=0.902).
The frequency of A-allele occurrence of CYP3A5*3 in Russian population is very poor, and it has no high influence on the safety of haloperidol treatment; therefore, there are no reasons to take this polymorphism into account in patients with alcohol addiction who receive haloperidol.
同工酶CYP2D6和CYP3A4的活性差异很大，参与氟哌啶醇的代谢，可能影响其疗效和安全性。
本研究的主要目的是评估CYP3A5基因多态性、CYP3A同工酶活性与酒精滥用患者使用氟哌啶醇发生药物不良反应风险之间的关系。
66名男性酒精成瘾患者参与了本研究。采用乌普萨拉监测中心副作用评定量表（UKU）和锥体外系症状辛普森-安格斯量表（SAS）评估氟哌啶醇的安全性。通过测定该同工酶的内源性底物（皮质醇）及其尿代谢产物（6-β-羟基皮质醇，6-B-HC）的浓度来评估CYP3A的活性。采用等位基因特异性杂交实时聚合酶链反应对CYP3A5*3进行基因分型。
俄罗斯人群中A等位基因的出现频率很低（2.27%）。CYP3A53多态性对氟哌啶醇的安全性指标没有影响（UKU量表：P=0.55，SAS量表：P=0.64）。此外，不同CYP3A53基因型组的代谢率（6-B-HC/皮质醇）指标值之间无统计学显著差异：GG组为5.00（3.36；6.39），AG组为5.26（2.10；6.78）（P=0.902）。
俄罗斯人群中CYP3A5*3的A等位基因出现频率很低，对氟哌啶醇治疗的安全性影响不大；因此，在接受氟哌啶醇治疗的酒精成瘾患者中没有必要考虑这种多态性。
