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

Relationship of the 1846G > A Polymorphism of the CYP2D6 Gene to the Equilibrium Concentration Levels of Haloperidol in Patients with Acute Alcoholic Hallucinosis

A A Parkhomenko¹, M S Zastrozhin², VYu Skryabin³, A E Petukhov⁴, S A Pozdniakov⁵, V A Ivanchenko⁶, I A Zaytsev⁷, I V Bure⁸, P O Bochkov⁹, K A Akmalova¹⁰, V V Smirnov¹¹, E A Bryun¹², D A Sychev¹³

Affiliations

¹ 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.
² Zastrozhin, PhD, MD, Associate professor of addiction psychiatry department.
³ Skryabin, PhD, MD, head of clinical department; Associate professor of addiction psychiatry department.
⁴ Petukhov, PhD, MD, clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring; associate professor of pharmaceutical and toxicological chemistry, Moscow, Russia.
⁵ Pozdniakov, researcher of the laboratory of genetics and fundamental studies.
⁶ Ivanchenko, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia.
⁷ Zaytsev, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia.
⁸ Bure, Senior Researcher, Predictive and Prognostic Biomarkers Department, Research Institute of Molecular and Personalized Medicine.
⁹ Bochkov, Senior Researcher, Predictive and Prognostic Biomarkers Department, Research Institute of Molecular and Personalized Medicine.
¹⁰ Akmalova, Researcher at the Department of Predictive and Prognostic Biomarkers of the Research Institute of Molecular and Personalized Medicine.
¹¹ Smirnov, Dr. Pharm. Sc, Head of the scientific and production complex FGBU "SSC Institute of Immunology" FMBA of Russia, National Research Center-Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russian Federation.
¹² Bryun, PhD, MD, professor, president, head of addiction psychiatry department.
¹³ Sychev, corresponding member of the Academy of Sciences of Russia, MD, PhD, professor, rector, head of clinical pharmacology and therapy department, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation.

PMID: 38076663
PMCID: PMC10698856

Relationship of the 1846G > A Polymorphism of the CYP2D6 Gene to the Equilibrium Concentration Levels of Haloperidol in Patients with Acute Alcoholic Hallucinosis

A A Parkhomenko et al. Psychopharmacol Bull. 2023.

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

Authors

Affiliations

¹ 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.
² Zastrozhin, PhD, MD, Associate professor of addiction psychiatry department.
³ Skryabin, PhD, MD, head of clinical department; Associate professor of addiction psychiatry department.
⁴ Petukhov, PhD, MD, clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring; associate professor of pharmaceutical and toxicological chemistry, Moscow, Russia.
⁵ Pozdniakov, researcher of the laboratory of genetics and fundamental studies.
⁶ Ivanchenko, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia.
⁷ Zaytsev, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia.
⁸ Bure, Senior Researcher, Predictive and Prognostic Biomarkers Department, Research Institute of Molecular and Personalized Medicine.
⁹ Bochkov, Senior Researcher, Predictive and Prognostic Biomarkers Department, Research Institute of Molecular and Personalized Medicine.
¹⁰ Akmalova, Researcher at the Department of Predictive and Prognostic Biomarkers of the Research Institute of Molecular and Personalized Medicine.
¹¹ Smirnov, Dr. Pharm. Sc, Head of the scientific and production complex FGBU "SSC Institute of Immunology" FMBA of Russia, National Research Center-Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russian Federation.
¹² Bryun, PhD, MD, professor, president, head of addiction psychiatry department.
¹³ Sychev, corresponding member of the Academy of Sciences of Russia, MD, PhD, professor, rector, head of clinical pharmacology and therapy department, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation.

PMID: 38076663
PMCID: PMC10698856

Abstract

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: GG genotype (-13.00 [-16.00; -16.00; -11.00]), GA 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: GG genotype (8.00 [7.00; 10.00]), GA genotype (15.00 [9.25; 18.00], p < 0.001); dynamics of the SAS score: GG genotype (11.00 [9.00; 14.00]), GA genotype (14.50 [12.00; 18.00], p < 0.001). The pharmacokinetic study results showed a statistically significant difference: GG (3.13 [2.32; 3.95]), GA (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 1846G > A polymorphism of the CYP2D6 gene (rs3892097) 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 GG and AG genotypes.

Conclusion: It can be concluded that patients with the GA genotype have a higher risk of ADRs compared to patients carrying the GG genotype. It is shown that 1846G > A polymorphism of the CYP2D6 gene (rs3892097) has a statistically significant effect on the equilibrium concentration levels of haloperidol.

Keywords: CYP2D6; acute alcoholic hallucinosis; equilibrium concentration; haloperidol; personalized medicine; pharmacogenetics.

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Figures

**Figure 1**
Effect of the *1846G* > A Polymorphism of the *CYP2D6* Gene (*RS3892097*) on the Equilibrium Concentration Levels of Haloperidol

See this image and copyright information in PMC

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Relationship of the 1846G > A Polymorphism of the CYP2D6 Gene to the Equilibrium Concentration Levels of Haloperidol in Patients with Acute Alcoholic Hallucinosis

Affiliations

Relationship of the 1846G > A Polymorphism of the CYP2D6 Gene to the Equilibrium Concentration Levels of Haloperidol in Patients with Acute Alcoholic Hallucinosis

Authors

Affiliations

Abstract

Figures

References

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Full Text Sources

Medical