Impact of Polymorphism of CYP2D6 on Equilibrium Concentration of Duloxetine in Patients Suffering from Major Depressive Disorder.

Autor:	Zastrozhin; MS Zastrozhin, M.D., PhD, head of laboratory of genetics and fundamental studies, AE Petukhov, M.D., PhD, clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, EP Pankratenko, paramedic-laboratory assistant of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, VYu Skryabin, M.D., head of clinical department, SG Koporov, M.D., PhD, director, EA Bryun, M.D., PhD, professor, president, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. MS Zastrozhin, associate professor of addiction psychiatry department, EA Grishina, PhD, head of biomolecular researchers department of the Research center, KA Ryzhikova, research fellow of the biomolecular researchers department of the Research center, EA Bryun, M.D., PhD, professor, president, DA Sychev, corresponding member of the Academy of Sciences of Russia, M.D., PhD, professor, rector, head of clinical pharmacology and therapy department, Moscow Research and Practical Centre on Addictions of the Moscow Department of Moscow, Russia. AE Petukhov, associate professor of pharmaceutical and toxicological chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation., Petukhov; MS Zastrozhin, M.D., PhD, head of laboratory of genetics and fundamental studies, AE Petukhov, M.D., PhD, clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, EP Pankratenko, paramedic-laboratory assistant of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, VYu Skryabin, M.D., head of clinical department, SG Koporov, M.D., PhD, director, EA Bryun, M.D., PhD, professor, president, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. MS Zastrozhin, associate professor of addiction psychiatry department, EA Grishina, PhD, head of biomolecular researchers department of the Research center, KA Ryzhikova, research fellow of the biomolecular researchers department of the Research center, EA Bryun, M.D., PhD, professor, president, DA Sychev, corresponding member of the Academy of Sciences of Russia, M.D., PhD, professor, rector, head of clinical pharmacology and therapy department, Moscow Research and Practical Centre on Addictions of the Moscow Department of Moscow, Russia. AE Petukhov, associate professor of pharmaceutical and toxicological chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation., Pankratenko; MS Zastrozhin, M.D., PhD, head of laboratory of genetics and fundamental studies, AE Petukhov, M.D., PhD, clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, EP Pankratenko, paramedic-laboratory assistant of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, VYu Skryabin, M.D., head of clinical department, SG Koporov, M.D., PhD, director, EA Bryun, M.D., PhD, professor, president, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. MS Zastrozhin, associate professor of addiction psychiatry department, EA Grishina, PhD, head of biomolecular researchers department of the Research center, KA Ryzhikova, research fellow of the biomolecular researchers department of the Research center, EA Bryun, M.D., PhD, professor, president, DA Sychev, corresponding member of the Academy of Sciences of Russia, M.D., PhD, professor, rector, head of clinical pharmacology and therapy department, Moscow Research and Practical Centre on Addictions of the Moscow Department of Moscow, Russia. AE Petukhov, associate professor of pharmaceutical and toxicological chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation., Grishina; MS Zastrozhin, M.D., PhD, head of laboratory of genetics and fundamental studies, AE Petukhov, M.D., PhD, clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, EP Pankratenko, paramedic-laboratory assistant of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, VYu Skryabin, M.D., head of clinical department, SG Koporov, M.D., PhD, director, EA Bryun, M.D., PhD, professor, president, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. MS Zastrozhin, associate professor of addiction psychiatry department, EA Grishina, PhD, head of biomolecular researchers department of the Research center, KA Ryzhikova, research fellow of the biomolecular researchers department of the Research center, EA Bryun, M.D., PhD, professor, president, DA Sychev, corresponding member of the Academy of Sciences of Russia, M.D., PhD, professor, rector, head of clinical pharmacology and therapy department, Moscow Research and Practical Centre on Addictions of the Moscow Department of Moscow, Russia. AE Petukhov, associate professor of pharmaceutical and toxicological chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation., Ryzhikova; MS Zastrozhin, M.D., PhD, head of laboratory of genetics and fundamental studies, AE Petukhov, M.D., PhD, clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, EP Pankratenko, paramedic-laboratory assistant of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, VYu Skryabin, M.D., head of clinical department, SG Koporov, M.D., PhD, director, EA Bryun, M.D., PhD, professor, president, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. MS Zastrozhin, associate professor of addiction psychiatry department, EA Grishina, PhD, head of biomolecular researchers department of the Research center, KA Ryzhikova, research fellow of the biomolecular researchers department of the Research center, EA Bryun, M.D., PhD, professor, president, DA Sychev, corresponding member of the Academy of Sciences of Russia, M.D., PhD, professor, rector, head of clinical pharmacology and therapy department, Moscow Research and Practical Centre on Addictions of the Moscow Department of Moscow, Russia. AE Petukhov, associate professor of pharmaceutical and toxicological chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation., Skryabin; MS Zastrozhin, M.D., PhD, head of laboratory of genetics and fundamental studies, AE Petukhov, M.D., PhD, clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, EP Pankratenko, paramedic-laboratory assistant of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, VYu Skryabin, M.D., head of clinical department, SG Koporov, M.D., PhD, director, EA Bryun, M.D., PhD, professor, president, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. MS Zastrozhin, associate professor of addiction psychiatry department, EA Grishina, PhD, head of biomolecular researchers department of the Research center, KA Ryzhikova, research fellow of the biomolecular researchers department of the Research center, EA Bryun, M.D., PhD, professor, president, DA Sychev, corresponding member of the Academy of Sciences of Russia, M.D., PhD, professor, rector, head of clinical pharmacology and therapy department, Moscow Research and Practical Centre on Addictions of the Moscow Department of Moscow, Russia. AE Petukhov, associate professor of pharmaceutical and toxicological chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation., Koporov; MS Zastrozhin, M.D., PhD, head of laboratory of genetics and fundamental studies, AE Petukhov, M.D., PhD, clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, EP Pankratenko, paramedic-laboratory assistant of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, VYu Skryabin, M.D., head of clinical department, SG Koporov, M.D., PhD, director, EA Bryun, M.D., PhD, professor, president, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. MS Zastrozhin, associate professor of addiction psychiatry department, EA Grishina, PhD, head of biomolecular researchers department of the Research center, KA Ryzhikova, research fellow of the biomolecular researchers department of the Research center, EA Bryun, M.D., PhD, professor, president, DA Sychev, corresponding member of the Academy of Sciences of Russia, M.D., PhD, professor, rector, head of clinical pharmacology and therapy department, Moscow Research and Practical Centre on Addictions of the Moscow Department of Moscow, Russia. AE Petukhov, associate professor of pharmaceutical and toxicological chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation., Bryun; MS Zastrozhin, M.D., PhD, head of laboratory of genetics and fundamental studies, AE Petukhov, M.D., PhD, clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, EP Pankratenko, paramedic-laboratory assistant of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, VYu Skryabin, M.D., head of clinical department, SG Koporov, M.D., PhD, director, EA Bryun, M.D., PhD, professor, president, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. MS Zastrozhin, associate professor of addiction psychiatry department, EA Grishina, PhD, head of biomolecular researchers department of the Research center, KA Ryzhikova, research fellow of the biomolecular researchers department of the Research center, EA Bryun, M.D., PhD, professor, president, DA Sychev, corresponding member of the Academy of Sciences of Russia, M.D., PhD, professor, rector, head of clinical pharmacology and therapy department, Moscow Research and Practical Centre on Addictions of the Moscow Department of Moscow, Russia. AE Petukhov, associate professor of pharmaceutical and toxicological chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation., Sychev; MS Zastrozhin, M.D., PhD, head of laboratory of genetics and fundamental studies, AE Petukhov, M.D., PhD, clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, EP Pankratenko, paramedic-laboratory assistant of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, VYu Skryabin, M.D., head of clinical department, SG Koporov, M.D., PhD, director, EA Bryun, M.D., PhD, professor, president, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. MS Zastrozhin, associate professor of addiction psychiatry department, EA Grishina, PhD, head of biomolecular researchers department of the Research center, KA Ryzhikova, research fellow of the biomolecular researchers department of the Research center, EA Bryun, M.D., PhD, professor, president, DA Sychev, corresponding member of the Academy of Sciences of Russia, M.D., PhD, professor, rector, head of clinical pharmacology and therapy department, Moscow Research and Practical Centre on Addictions of the Moscow Department of Moscow, Russia. AE Petukhov, associate professor of pharmaceutical and toxicological chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation.
Jazyk:	angličtina
Zdroj:	Psychopharmacology bulletin [Psychopharmacol Bull] 2020 Jul 23; Vol. 50 (3), pp. 47-57.
Abstrakt:	Introduction: Duloxetine is commonly prescribed to patients with recurrent depressive disorder. Some part of patients in this group do not respond adequately to treatment regimen containing duloxetine, while many of them experience dose-dependent adverse drug reactions. Previous research investigated that CYP2D6 is involved in the biotransformation of duloxetine, the activity of which is highly dependent on the polymorphism of the gene encoding it. Objective: The objective of this study was to evaluate the influence of 1846G > A polymorphism of the CYP2D6 gene on the concentration/dose indicator of duloxetine, using findings on enzymatic activity of CYP2D6 (as evaluated by the 6M-THBC/pinoline ratio measurement) and on CYP2D6 expression level obtained by measuring the hsa-miR-370-3p plasma concentration levels in patients suffering from recurrent depressive disorder. Material and Methods: This study enrolled 118 patients with recurrent depressive disorder (average age - 40.6±17.1 years). Therapy included duloxetine in an average daily dose of 103.7±37.1 mg per day. Treatment efficacy was assessed using the international psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping we performed the real-time polymerase chain reaction (PCR Real-time). Therapeutic drug monitoring has been performed using HPLC-MS/MS. Results: Our findings revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMD scores at the end of the treatment course): (GG) 9.0 [7.0; 10.0] and (GA) 11.0 [8.5; 14.0], p < 0.001; at the same time, the statistical significance in the safety profile was obtained (the UKU scores): (GG) 3.0 [3.0; 4.0] and (GA) 4.0 [3.0; 4.0], p = 0.007. We revealed a statistical significance for concentration/dose indicator of duloxetine in patients with different genotypes: (GG) 0.776 [0.529; 1.067] and (GA) 1.388 [0.942; 1.732], p < 0.001. Conclusion: Thus, the effect of genetic polymorphism of the CYP2D6 gene on the efficacy and safety profiles of duloxetine was demonstrated in a group of 118 patients with recurrent depressive disorder. Competing Interests: Funding Source This work was supported by the grant of the Russian Science Foundation (project No. 18-75-10073). Disclosure The authors report no conflicts of interest in this work. (Copyright © 1964–2019 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)
Databáze:	MEDLINE
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