Полиморфизм 3435c>T гена ABCB1 (rs1045642) не влияет на профиль эффективности и безопасности миртазипина у пациентов с депрессивными расстройствами, коморбидными с алкогольной зависимостью

Background. Mirtazapine is used to treat patients with depressive disorders. A large proportion of patients in this group do not adequately respond to mirtazapine therapy, while many develop undesirable drug reactions of type A. According to the previous studies, P-gp is involved in the biotransformation of mirtazapine, the activity of which is highly dependent on the polymorphism of the gene encoding it.Aim. The aim of our study was to study the effect of mirtazapine gene polymorphism on the efficacy and safety of mirtazapine therapy in patients with depressive disorders, comorbid with alcohol dependence.Materials and methods. The study included 119 male patients with depressive disorders, comorbid with alcohol dependence (age 38.7 ± 16.0 years). As a therapy, mirtazapine was used at a dose of 37.8 ± 13.8 mg / day. Evaluation of the effectiveness profile was carried out using psychometric scales. The safety profile was evaluated using the UKU Side-Effect Rating Scale. Genotyping was carried out by polymerase chain reaction in real time.Results. In the course of the study, results statistically significant in terms of evaluating efficacy and safety were not obtained (HAMD scores at the end of the course of therapy: (CC) 2.5 [2.0; 4.0], (CT) 2.0 [ 1.0; 3.0] and (TT) 2.0 [1.0; 3.0], p > 0.999; according to the UKU scale: (CC) 3.0 [2.8; 3.0], ( CT) 3.0 [3.0; 3.0] and (TT) 3.0 [3.0; 3.0], p > 0.999).Conclusion. The study of 119 patients with depressive disorders comorbid with alcohol dependence showed that 3435C> T polymorphism of the ABCB1 gene (rs1045642) does not affect the clinical efficacy and safety of mirtazapine.Введение. Миртазапин используется для лечения пациентов с депрессивными расстройствами. Немалая доля пациентов данной группы не отвечает должным образом на терапию миртазапином, при этом у многих отмечается развитие нежелательных лекарственных реакций типа А. По результатам ранее проводимых исследований показано, что в биотрансформации миртазапина принимает участие гликопротеин P, активность которого в высокой степени зависит от полиморфизма кодирующего его гена.Цель. Изучить влияние полиморфизма гена ABCB1 на эффективность и безопасность  терапии миртазапином у пациентов с депрессивными расстройствами, коморбидными с  алкогольной зависимостью. Материалы и методы. В исследование было включено 119 пациентов мужского пола с депрессивными расстройствами, коморбидными с алкогольной зависимостью (средний возраст (38,7 ± 16,0) лет). В качестве терапии использовали миртазапин в дозе (37,8 ± 13,8) мг/сут. Оценка профиля эффективности производилась с помощью  психометрических шкал. Профиль безопасности оценивался с помощью  валидизированной шкалы UKU Side-Effect Rating Scale. Генотипирование проводилось методом полимеразной цепной реакции в режиме реального времени.Результаты. По результатам исследования не получены статистически значимые результаты в показателях оценки эффективности и безопасности (баллы по шкале HAMD в концу курса терапии: (CC) 2,5 [2,0; 4,0], (CT) 2,0 [1,0; 3,0] и (TT) 2,0 [1,0; 3,0], p > 0,999; по шкале UKU: (CC) 3,0 [2,8; 3,0], (CT) 3,0 [3,0; 3,0] и (TT) 3,0 [3,0; 3,0], p > 0,999).Заключение. Продемонстрировано отсутствие влияния полиморфизма 3435C>T гена ABCB1 (rs1045642) на показатель клинической эффективности и безопасности миртазапина

Association between the activity of enzyme CYP3A4 and profile of efficacy and safety of haloperidol in patiens with alcohol addiction

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. Microsomal isozyme cytochrome P450 3A4, the activity of which has wide variability, takes part in biotransformation of haloperidol. The study involved 35 men with alcohol addiction. The efficacy and safety of haloperidol was evaluated by international psychometric scales. The activity of CYP3A4 was evaluated by determination endogenous substrate of this isoenzyme and its metabolite in urine - (the ratio of 6-beta-hydrocortizol/corizol). The study revealed a statistically significant patterns between the activity of CYP3A4 and the efficacy and safety of haloperidol

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

Association between the activity of enzyme CYP3A4 and profile of efficacy and safety of haloperidol in patiens with alcohol addiction

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. Microsomal isozyme cytochrome P450 3A4, the activity of which has wide variability, takes part in biotransformation of haloperidol. The study involved 35 men with alcohol addiction. The efficacy and safety of haloperidol was evaluated by international psychometric scales. The activity of CYP3A4 was evaluated by determination endogenous substrate of this isoenzyme and its metabolite in urine - (the ratio of 6-beta-hydrocortizol/corizol). The study revealed a statistically significant patterns between the activity of CYP3A4 and the efficacy and safety of haloperidol

The relationship between the CYP2C19*17 genetic polymorphism and the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome

The aim of our study was to study the relationship between the CYP2C19 genetic polymorphism and the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome in order to develop algorithms for optimizing the therapy of diazepam to reduce the risk of dose-dependent adverse drug reactions and pharmacoresistance.Materials and methods. The study was conducted on 30 Russian male patients suffering from alcohol withdrawal syndrome. For the treatment of anxiety, fear and emotional tension, patients received diazepam in injections at a dosage of 30,0 mg / day for 5 days. Genotyping was performed by real-time polymerase chain reaction with allele-specific hybridization. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions: the Clinical Institute Withdrawal Assessment for Alcohol scale, the visual-analogue scale of the craving for alcohol, and the side-effect scale.Results. Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 -806C>T genotypes: (CC) –12,0 [–15,0; –8,0], (CT + TT) –7.0 [–14,0; –5,0], p = 0,001. The scores on the UKU scale, which was used to evaluate the safety of therapy, were also different: (CC) 8,0 [6,0; 12,0], (CT + TT) 6,0 [6,0; 12,0], p = 0,006.Conclusion. The relationships between the CYP2C19 genetic polymorphism and the efficacy and safety of diazepam were demonstrated. This should be taken into consideration when prescribing this drug to such patients in order to reduce the risk of adverse drug reactions and pharmacoresistance

Effects of CYP2C19 genetic polymorphism on the steady-state concentration of citalopram in patients with major depressive disorder

Copyright © 2021, The Author(s), under exclusive licence to Springer Nature Limited part of Springer NatureCitalopram is commonly prescribed to patients suffering from major depressive disorder. Some of them do not respond adequately to therapy with citalopram, while many of them experience type A adverse drug reactions. Current research revealed that CYP2C19 isoenzyme is involved in the biotransformation of citalopram. The objective of our study was to investigate the impact of 681G>A polymorphism of the CYP2C19 gene on the efficacy, safety and the concentration/dose indicator of citalopram. Our study enrolled 130 patients with major depressive disorder and comorbid alcohol use disorder (average age-38.7 ± 14.1 years). Therapy regimen included citalopram in an average daily dose of 31.1 ± 14.4 mg per week. Therapy efficacy and safety were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Our findings revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMD scores at the end of the treatment course): (GG) 8.0 [8.0; 9.0] and (GA) 10.0 [9.0; 11.0], p < 0.001. In the safety profile (the UKU scores), the statistical significance was also obtained: (GG) 3.0 [3.0; 4.0] and (GA) 5.0 [4.0; 5.0], p < 0.001. We revealed a statistical significance for concentration/dose indicator of citalopram in patients with different genotypes: (GG) 2.543 [1.659; 4.239] and (GA) 4.196 [2.643; 5.753], p < 0.001). The effect of CYP2C19 genetic polymorphism on the efficacy and safety profiles of citalopram was demonstrated in a group of 130 patients with major depressive disorder.info:eu-repo/semantics/publishedVersio

How do CYP2C19*2 and CYP2C19*17 genetic polymorphisms affect the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome?

© 2020 Walter de Gruyter GmbH, Berlin/Boston.Background: Diazepam is one of the most commonly prescribed tranquilizers for therapy of alcohol withdrawal syndrome (AWS). Despite its popularity, there is currently no precise information on the effect of genetic polymorphisms on its efficacy and safety. The objective of our study was to investigate the effect of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy and safety of diazepam in patients with AWS. Methods: The study was conducted on 30 Russian male patients suffering from the AWS who received diazepam in injections at a dosage of 30.0 mg/day for 5 days. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 681G>A (CYP2C19*2, rs4244285) genotypes: (CYP2C19*1/*1) -8.5 [-15.0; -5.0], (CYP2C19*1/*2 and CYP2C19*2/*2) -12.0 [-13.0; -9.0], p = 0.021. The UKU scale scores, which were used to evaluate the safety of therapy, were also different: (CYP2C19*1/*1) 7.0 [6.0; 12.0], (CYP2C19*1/*2 and CYP2C19*2/*2) 9.5 [8.0; 11.0], p = 0.009. Patients carrying different CYP2C19 -806C>T (CYP2C19*17, rs12248560) genotypes also demonstrated differences in therapy efficacy and safety rates. Conclusions: Thus, the effects of CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the efficacy of diazepam were demonstrated.info:eu-repo/semantics/publishedVersio

Взаимосвязь полиморфизма CYP2C19*17 с показателями эффективности и безопасности диазепама у пациентов с синдромом отмены алкоголя

The aim of our study was to study the relationship between the CYP2C19 genetic polymorphism and the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome in order to develop algorithms for optimizing the therapy of diazepam to reduce the risk of dose-dependent adverse drug reactions and pharmacoresistance.Materials and methods. The study was conducted on 30 Russian male patients suffering from alcohol withdrawal syndrome. For the treatment of anxiety, fear and emotional tension, patients received diazepam in injections at a dosage of 30,0 mg / day for 5 days. Genotyping was performed by real-time polymerase chain reaction with allele-specific hybridization. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions: the Clinical Institute Withdrawal Assessment for Alcohol scale, the visual-analogue scale of the craving for alcohol, and the side-effect scale.Results. Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 -806C&gt;T genotypes: (CC) –12,0 [–15,0; –8,0], (CT + TT) –7.0 [–14,0; –5,0], p = 0,001. The scores on the UKU scale, which was used to evaluate the safety of therapy, were also different: (CC) 8,0 [6,0; 12,0], (CT + TT) 6,0 [6,0; 12,0], p = 0,006.Conclusion. The relationships between the CYP2C19 genetic polymorphism and the efficacy and safety of diazepam were demonstrated. This should be taken into consideration when prescribing this drug to such patients in order to reduce the risk of adverse drug reactions and pharmacoresistance. Цель исследования – изучение взаимосвязи полиморфизма гена CYP2C19 с показателямиэффективности и безопасности диазепама у пациентов с синдромом отмены алкоголя дляснижения риска развития дозозависимых нежелательных лекарственных реакций (НЛР) ифармакорезистентности.Материалы и методы. Исследование проведено на 30 русских пациентах мужского пола (среднийвозраст – (44,6 ± 10,4) года) с установленным диагнозом синдрома отмены алкоголя. Пациентыс целью терапии аффекта тревоги, страха и эмоциональной напряженности в рамках синдромаотмены алкоголя получали в течение 5 сут диазепам в форме раствора для внутримышечных и внутривенных инъекций в дозировке 30 мг/сут. Генотипирование производилось методом полимеразной цепной реакции в режиме реального времени с аллель-специфической гибридизацией. Оценкаэффективности и безопасности осуществлялась с помощью психометрических шкал и шкал оценкивыраженности НЛР: международной шкалы оценки тяжести синдрома отмены алкоголя CIWA-Ar,визуально-аналоговой шкалы оценки влечения к алкоголю, шкалы оценки побочного действия.Результаты. Установлены различия в показателе эффективности терапии у пациентов с разнымигенотипами по полиморфному маркеру -806C&gt;T гена CYP2C19: (CC) –12,0 [–15,0; –8,0], (CT + TT)–7,0 [–14,0; –5,0], p = 0,001. Баллы по шкале UKU, с помощью которой оценивалась безопасность,также различались: (CC) 8,0 [6,0; 12,0], (CT + TT) 6,0 [6,0; 12,0], p = 0,006.Заключение. Показано, что полиморфизм гена CYP2C19 может быть связан с показателямиэффективности и безопасности терапии диазепамом у пациентов с синдромом отмены алкоголя. Этонеобходимо учитывать при назначении данного лекарственного средства таким пациентам с цельюснижения риска развития нежелательных реакций и фармакорезистентности

Harmful alcohol use among acutely ill hospitalized medical patients in Oslo and Moscow: A cross-sectional study

Background The aim was to estimate the prevalence of harmful alcohol use in relation to socio-demographic characteristics among acutely ill medical patients, and examine identification measures of alcohol use, including the alcohol biomarker phosphatidylethanol 16:0/18:1 (PEth). Methods A cross-sectional study, lasting one year at one hospital in Oslo, Norway and one in Moscow, Russia recruiting acute medically ill patients (≥ 18 years), able to give informed consent. Self-reported data on socio-demographics, mental distress (Symptom Check List-5), alcohol use (Alcohol Use Disorder Identification Test-4 (AUDIT-4) and alcohol consumption past 24 h were collected. PEth and alcohol concentration were measured in whole blood. Results Of 5883 participating patients, 19.2% in Moscow and 21.1% in Oslo were harmful alcohol users, measured by AUDIT-4, while the prevalence of PEth-positive patients was lower: 11.4% in Oslo, 14.3% in Moscow. Men in Moscow were more likely to be harmful users by AUDIT-4 and PEth compared to men in Oslo, except of those being ≥ 71 years. Women in Oslo were more likely to be harmful users compared to those in Moscow by AUDIT-4, but not by PEth for those aged < 61 years. Conclusions The prevalence of harmful alcohol use was high at both study sites. The prevalence of harmful alcohol use was lower when assessed by PEth compared to AUDIT-4. Thus, self-reporting was the most sensitive measure in revealing harmful alcohol use among all groups except for women in Moscow. Hence, screening and identification with objective biomarkers and self-reporting might be a method for early intervention