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. 2017 Dec 28:11:1-5.
doi: 10.2147/PGPM.S144503. eCollection 2018.

The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with alcohol addiction

Mikhail Sergeevich Zastrozhin  1   2 , Elena Anatolievna Grishina  1 , Kristina Anatolievna Ryzhikova  1 , Valery Valerievich Smirnov  3 , Ludmila Mikhailovna Savchenko  1 , Evgeny Alekseevich Bryun  1   2 , Dmitry Alekseevich Sychev  1
Affiliations

The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with alcohol addiction

Mikhail Sergeevich Zastrozhin et al. Pharmgenomics Pers Med. .

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: The frequency of A-allele occurrence in Russian population was very poor (2.27%). CYP3A5*3 polymorphism had no influence on safety profile indicators of haloperidol (UKU scale: p=0.55, SAS scale: p=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 CYP3A5*3: GG 5.00 (3.36; 6.39) vs AG 5.26 (2.10; 6.78) (p=0.902).

Conclusion: 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.

Keywords: CYP3A; CYP3A5*; alcohol use disorder; cortisol; haloperidol.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Metabolic 6-B-HC/cortisol ratio in patients with genotypes of GG and AG on a polymorphic marker 6986A>G of CYP3A5 gene. Abbreviations: 6-B-HC, 6-beta-hydroxycortisol; cu, conditional units.
Figure 2
Figure 2
Relationship between the activity of CYP3A and difference in scores on UKU scale in patients receiving haloperidol in injection form. Abbreviations: 6-B-HC, 6-beta-hydroxycortisol; UKU, Udvalg for Kliniske Undersogelser Side Effect Rating Scale.
See this image and copyright information in PMC

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