A A Parkhomenko1, M S Zastrozhin1, VYu Skryabin1, V A Ivanchenko1, S A Pozdniakov1, V V Noskov1, I A Zaytsev1, N P Denisenko1, K A Akmalova1, E A Bryun1, D A Sychev1. 1. Parkhomenko, Postgraduate student in the Department of Addiction Medicine, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia. Zastrozhin, PhD, M.D., Postdoctoral Fellow, University of California, San Francisco, CA, USA. Skryabin, PhD, M.D., head of clinical department, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia; Associate professor of addiction psychiatry department, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia. Ivanchenko, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia. Pozdniakov, researcher of the laboratory of genetics and fundamental studies, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia. Noskov, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia. Zaytsev, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia. Denisenko, PhD in Medicine, Head of the Department of Personalized Medicine, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia. Akmalova, Researcher in the Department of Molecular Medicine, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia. Bryun, PhD, M.D., professor, president, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia; head of addiction psychiatry department, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russia. Sychev, corresponding member of the Academy of Sciences of Russia, M.D., 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, Russia.
Abstract
Background: Previous studies have shown that haloperidol biotransformation occurs with participation of the CYP2D6 isoenzyme. The CYP2D6 gene is highly polymorphic, which may contribute to differences in its activity and in the haloperidol biotransformation rates across different individuals, resulting in variable drug efficacy and safety profiles. Purpose: The study aimed to investigate the correlation of the 1846G> A polymorphism of CYP2D6 gene with the efficacy and safety rates of haloperidol in patients with alcoholic hallucinoses. Material and methods: One hundred male patients received 5-10 mg/day haloperidol by injections for 5 days. The efficacy and safety assessments were performed using the validated psychometric scales PANSS, UKU, and SAS. For genotyping, the real-time polymerase chain reaction was performed. Results: We revealed no statistically significant results in terms of haloperidol efficacy in patients with different genotypes (dynamics of the PANSS scores: (GG) -13.00 [-16.00; -11.00], (GA) -15.00 [-16.75; -13.00], p = 0,728). Our findings revealed the statistically significant results in terms of treatment 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. Conclusion: These results suggest that genotyping for common CYP3A variants might have the potential to guide benzodiazepine withdrawal treatment. The effect of of the 1846G>A polymorphism of CYP2D6 gene on the safety profile of haloperidol was demonstrated in a group of 100 patients with alcoholic hallucinoses.
Background: Previous studies have shown that haloperidol biotransformation occurs with participation of the CYP2D6 isoenzyme. The CYP2D6 gene is highly polymorphic, which may contribute to differences in its activity and in the haloperidol biotransformation rates across different individuals, resulting in variable drug efficacy and safety profiles. Purpose: The study aimed to investigate the correlation of the 1846G> A polymorphism of CYP2D6 gene with the efficacy and safety rates of haloperidol in patients with alcoholic hallucinoses. Material and methods: One hundred male patients received 5-10 mg/day haloperidol by injections for 5 days. The efficacy and safety assessments were performed using the validated psychometric scales PANSS, UKU, and SAS. For genotyping, the real-time polymerase chain reaction was performed. Results: We revealed no statistically significant results in terms of haloperidol efficacy in patients with different genotypes (dynamics of the PANSS scores: (GG) -13.00 [-16.00; -11.00], (GA) -15.00 [-16.75; -13.00], p = 0,728). Our findings revealed the statistically significant results in terms of treatment 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. Conclusion: These results suggest that genotyping for common CYP3A variants might have the potential to guide benzodiazepine withdrawal treatment. The effect of of the 1846G>A polymorphism of CYP2D6 gene on the safety profile of haloperidol was demonstrated in a group of 100 patients with alcoholic hallucinoses.
Authors: Jürgen Brockmöller; Julia Kirchheiner; Jürgen Schmider; Silke Walter; Christoph Sachse; Bruno Müller-Oerlinghausen; Ivar Roots Journal: Clin Pharmacol Ther Date: 2002-10 Impact factor: 6.875