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. 2022 Oct 27;52(4):52-60.

Association of CYP2D6*4 Polymorphism with the Steady-State Concentration of Haloperidol in Patients with Alcohol-Induced Psychotic Disorders

A A Parkhomenko  1 , M S Zastrozhin  2 , S A Pozdnyakov  3 , V V Noskov  4 , I A Zaytsev  5 , V A Ivanchenko  6 , N P Denisenko  7 , K A Akmalova  8 , VYu Skryabin  9 , E A Bryun  10 , D A Sychev  11
Affiliations

Association of CYP2D6*4 Polymorphism with the Steady-State Concentration of Haloperidol in Patients with Alcohol-Induced Psychotic Disorders

A A Parkhomenko et al. Psychopharmacol Bull. .

Abstract

Background: CYP2D6 subfamily isoenzymes play an important role in the biotransformation of haloperidol, and their activity may influence the efficacy and safety of haloperidol. The use of haloperidol is often associated with the occurrence of adverse drug reactions (ADRs), such as dyskinesia, acute dystonia, and orthostatic hypotension. Previous studies have demonstrated the relationship between the CYP2D6*4 genetic polymorphism and CYP2D6 activity, as well as haloperidol efficacy and safety rates.

Purpose: To evaluate the association of CYP2D6*4 genetic polymorphism with the steady-state concentration of haloperidol in patients with acute alcohol-induced psychotic disorders (AIPDs).

Material and methods: The study involved 100 male patients with AIPD (average age 41.4 ± 14.4 years) who received haloperidol by injections in a dose of 5-10 mg/day. The efficacy profile was assessed using a validated psychometric PANSS scale (Positive and Negative Syndrome Scale). Therapy safety was assessed using the internationally validated UKU (Side-Effect Rating Scale) and SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scales. Genotyping was performed with the real-time polymerase chain reaction.

Results: We revealed the statistically significant results in terms of therapy safety evaluation (dynamics of the UKU scores: (GG) 8.00 [7.00; 10.00], (GA) 15.0 [9.25; 18.0], p < 0.001; dynamics of the SAS scores: (GG) 11.0 [9.0; 14.0], (GA) 14.50 [12.0; 18.0], p < 0.001. Pharmacokinetic study showed a statistically significant difference across the groups with different genotypes: (GG) 3.13 [2.32; 3.95], (GA) 3.89 [2.92; 5.26], p = 0.010.

Conclusion: It can be concluded that patients with the GA genotype have a higher risk of ADRs compared to patients who carry the GG genotype. It was shown that CYP2D6*4 genetic polymorphism has a statistically significant effect on the steady-state concentration of haloperidol.

Keywords: CYP2D6; alcohol-induced psychotic disorders; haloperidol; personalized medicine; pharmacogenetics.

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Figures

Figure 1
Figure 1
Effect of CYP2D6*4 Genetic Polymorphism on Haloperidol Steady-State Concentration Levels
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