The correlation between CYP2D6 isoenzyme activity and haloperidol efficacy and safety profile in patients with alcohol addiction during the exacerbation of the addiction.
BACKGROUND
Today, it is proved that isoenzymes CYP2D6 and CYP3A4 are involved in metabolism of haloperidol. In our previous investigation, we found a medium correlation between the efficacy and safety of haloperidol and the activity of CYP3A4 in patients with alcohol abuse.


OBJECTIVE
The aim of this study was to evaluate the correlation between the activity of CYP2D6 and the efficacy and safety of haloperidol in patients with diagnosed alcohol abuse.


METHODS
The study involved 70 men (average age: 40.83±9.92 years) with alcohol addiction. A series of psychometric scales were used in the research. The activity of CYP2D6 was evaluated by high-performance liquid chromatography with mass spectrometry using the ratio of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline to pinoline. Genotyping of CYP2D6 (1846G>A) was performed using real-time polymerase chain reaction.


RESULTS
According to results of correlation analysis, statistically significant values of Spearman correlation coefficient (rs) between the activity of CYP2D6 and the difference of points in psychometric scale were obtained in patients receiving haloperidol in injection form (Sheehan Clinical Anxiety Rating Scale =-0.721 [P<0.001] and Udvald for Kliniske Undersogelser Side Effect Rating Scale =0.692 [P<0.001]) and in those receiving haloperidol in tablet form (Covi Anxiety Scale =-0.851 [P<0.001] and Udvald for Kliniske Undersogelser Side Effect Rating Scale =0.797 [P<0.001]).


CONCLUSIONS
This study demonstrated the correlations between the activity of CYP2D6 isozyme and the efficacy and safety of haloperidol in patients with alcohol addiction.
Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation.
Dmitry Alekseevich
DA
Sychev
Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation; Department of Public Health, Moscow Research and Practical Centre for Narcology; Peoples' Friendship University of Russia.
Mikhail Sergeevich
MS
Zastrozhin
National Research Center, Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia.
Valery Valerieevich
VV
Smirnov
Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation.
Elena Anatolievna
EA
Grishina
Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation.
Ludmila Mikhailovna
LM
Savchenko
Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation; Department of Public Health, Moscow Research and Practical Centre for Narcology.
Evgeny Alekseevich
EA
Bryun
CYP2D6; alcohol addiction; biotransformation; haloperidol; side effects
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