THE INVESTIGATION OF INFLUENCE OF GENETIC PROFILE ON THE EFFICACY AND SAFETY OF HALOPERIDOL IN PATIENTS WITH ALCOHOL DEPENDENCE

In case of patients with alcohol addiction haloperidol is used to control the exacerbation of the addiction, but the empirical dose selection of haloperidol often results in adverse side effects. Enzyme CYP2D6, which has encoded by gene CYP2D6 has high variability of activity, which depend from polymorphism of gene CYP2D6. P- glycoprotein, which has encoded by gene ABCB1 has high variability of activity, which depend from polymorphism of gene ABCB1. The study involved 20 men with alcohol addiction. The efficacy and safety of haloperidol was evaluated by international psychometric scales. The genotype of CYP2D6 was investigated by real-time PCR. The study revealed a statistically significant patterns between the polymorphism of CYP2D6 and the efficacy and safety of haloperidol. The genotype of ABCB1 was investigated by real-time PCR. The study revealed a statistically significant patterns between the polymorphism of ABCB1 and the efficacy and safety of haloperidol.

1. Сиволап Ю.П. Рациональные подходы к применению нейролептиков в наркологической практике. Здоровая Украина. 2008; 7/1: 83-84. Sivolap J.P. Rational approaches to the use of antipsychotic drugs in drug treatment practice. Healthy Ukraine. 2008; 7/1: 83-84.

2. Butwicka A., Krystyna S., Retka W., Wolańczyk T. Neuroleptic malignant syndrome in an adolescent with CYP2D6 deficiency. Eur. J. Pediatr. 2014;173(12):1639-1642.

3. Drescher S., Schaeffeler E., Hitzl M. et al. MDR1 gene polymorphisms and disposition of the P-glycoprotein substrate fexofenadine. Br. J. Clin. Pharmacol. 2002; 53(5): 526-534.

4. Gasso P., Papagianni K., Bobadilla R.F., Arnaiz J.A., Bernardo M., Lafuente A. Relationship between CYP2D6 genotype and haloperidol pharmacokinetics and extrapyramidal symptoms in healthy volunteers. Pharmacogenomics. 2013; 14(13): 1551-1563.

5. Hitzl M., Drescher S., Kuip H. et al. The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56+ natural killer cells. Pharmacogenetics. 2001; 11(4): 293-298.

6. Hoffmeyer S., Burk O., von Richter O. et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlations of one allele with P-glycoprotein expression and activity in vivo. Proc. Natl. Acad. Sci. USA. 2000; 97(7): 3473-3478.

7. Nakamura A., Mihara K., Ne moto K. et al. Lack of correlation between the steady-state plasma concentrations of aripiprazole and haloperidol in Japanese patients with schizophrenia. Ther. Drug. Monit. 2014; 36(6): 815-818.

8. Siegsmund M., Brinkmann U., Schaffeler E. et al. Association of the P-glycoprotein transporter MDR1(C3435T) polymorphisms with the susceptibility to tenal epithelial tumors. J. Am. Soc. Nephrol. 2002; 13(7): 1847-1854.

9. Van der Weide K., van der Weide J. The Influence of the CYP3A4*22 Polymorphism and CYP2D6 Polymorphisms on Serum Concentrations of Aripiprazole, Haloperidol. J. Clin. Psychopharmacol. 2015; 35(3): 228-236.

10. Zanger U.M., Raimundo S., Eichelbaum M. Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch. Pharmacol. 2004; 369(1): 23–37.