Genetic Testing is Superior Over Endogenous Pharmacometabolomic Markers to Predict Safety of Haloperidol in Patients with Alcohol-induced Psychotic Disorder.
| Autor: | Skryabin V; Department of Healthcare, Moscow Research and Practical Centre on Addictions of the Moscow, 37/1 Lyublinskaya Street, Moscow, 109390, Russia.; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, 2/1 Barrikadnaya Street, Moscow, 123995, Russian Federation., Zastrozhin M; Department of Healthcare, Moscow Research and Practical Centre on Addictions of the Moscow, 37/1 Lyublinskaya Street, Moscow, 109390, Russia.; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, 2/1 Barrikadnaya Street, Moscow, 123995, Russian Federation.; University of California, San Francisco, 1701 Divisadero St, San Francisco, CA 94115, USA., Parkhomenko A; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, 2/1 Barrikadnaya Street, Moscow, 123995, Russian Federation., Lauschke VM; Department of Physiology and Pharmacology, Karolinska Institutet, Solnavägen 1, 171 77 Solna, Sweden.; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstraße 112, 70376 Stuttgart, Germany.; University of Tuebingen, Geschwister-Scholl-Platz, 72074 Tuebingen, Germany., Smirnov V; I.M. Sechenov First Moscow State Medical University (Sechenov University), 8с2 Trubetskaya Street, Moscow, 119991, Russian Federation.; NRC Institute of Immunology FMBA of Russia, 24 Kashirskoe shosse, Moscow, 115478, Russian Federation., Petukhov A; M. Sechenov First Moscow State Medical University (Sechenov University), 8с2 Trubetskaya Street, Moscow, 119991, Russian Federation., Pankratenko E; Department of Healthcare, Moscow Research and Practical Centre on Addictions of the Moscow, 37/1 Lyublinskaya Street, Moscow, 109390, Russia., Pozdnyakov S; Department of Healthcare, Moscow Research and Practical Centre on Addictions of the Moscow, 37/1 Lyublinskaya Street, Moscow, 109390, Russia., Koporov S; Department of Healthcare, Moscow Research and Practical Centre on Addictions of the Moscow, 37/1 Lyublinskaya Street, Moscow, 109390, Russia., Denisenko N; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, 2/1 Barrikadnaya Street, Moscow, 123995, Russian Federation., Akmalova K; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, 2/1 Barrikadnaya Street, Moscow, 123995, Russian Federation., Bryun E; Department of Healthcare, Moscow Research and Practical Centre on Addictions of the Moscow, 37/1 Lyublinskaya Street, Moscow, 109390, Russia.; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, 2/1 Barrikadnaya Street, Moscow, 123995, Russian Federation., Sychev D; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, 2/1 Barrikadnaya Street, Moscow, 123995, Russian Federation. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Current drug metabolism [Curr Drug Metab] 2022; Vol. 23 (13), pp. 1067-1071. |
| DOI: | 10.2174/1389200224666221228112643 |
| Abstrakt: | Background: Previous studies have shown that haloperidol biotransformation is mainly metabolized by CYP2D6. The CYP2D6 gene is highly polymorphic, contributing to inter-individual differences in enzymatic activity, and may impact haloperidol biotransformation rates, resulting in variable drug efficacy and safety profiles. Objective: The study aimed to investigate the correlation of the CYPD6 activity with haloperidol's efficacy and safety rates in patients with alcohol-induced psychotic disorders. Methods: One hundred male patients received 5-10 mg/day haloperidol by injections for 5 days. The efficacy and safety assessments were performed using PANSS, UKU, and SAS-validated psychometric scales. Results: No relationship between haloperidol efficacy or safety and the experimental endogenous pharmacometabolomic marker for CYP2D6 activity, urinary 6-НО-ТНВС/pinoline ratio was identified. In contrast, we found a statistically significant association between haloperidol adverse events and the most common CYP2D6 loss-of-function allele CYP2D6*4 (p<0.001). Conclusion: Evaluation of the single polymorphism rs3892097 that defines CYP2D6*4 can predict the safety profile of haloperidol in patients with AIPD, whereas metabolic evaluation using an endogenous marker was not a suitable predictor. Furthermore, our results suggest haloperidol dose reductions could be considered in AIPD patients with at least one inactive CYP2D6 allele. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|