scholarly journals MicroRNA hsa-miR-370-3p is a new biomarker for assessing the level of CYP2D6 gene expression, as well as the clinical efficacy and safety of mirtazapine in patients with depressive disorders comorbid with alcohol use disorder

2020 ◽  
pp. 62-63
Author(s):  
М.С. Застрожин ◽  
В.Ю. Скрябин ◽  
Е.А. Гришина ◽  
К.А. Рыжикова ◽  
И.В. Буре ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasma Concentration ◽  
Gene Polymorphism ◽  
Clinical Efficacy ◽  
Safety Profile ◽  
Alcohol Use Disorder ◽  
Depressive Disorders ◽  
Polymorphic Marker ◽  
Efficacy And Safety ◽  
Cyp2d6 Gene

Проведено изучение влияния полиморфизма гена CYP2D6 на эффективность и безопасность терапии миртазапина у пациентов с депрессивными расстройствами, коморбидными с алкоголизмом. В группе из 106 пациентов с депрессивными расстройствами, коморбидными с алкогольной зависимостью, было продемонстрировано влияние полиморфизма 1846G>A гена CYP2D6 (rs3892097) на показатели профиля безопасности миртазапина, но не эффективности. При этом hsa-miR-370-3p остается перспективным биомаркером оценки уровня экспресии гена CYP2D6, так как уровень его плазменной концентрации отличался у носителей разных генотипов по полиморфному маркеру 1846G>A, хотя и не обнаружилась связь с клинической эффективностью и безопасностью. The study of the effect of CYP2D6 gene polymorphism on the efficacy and safety of mirtazapine therapy in patients with depressive disorders comorbid with alcoholism was carried out. In a group of 106 patients with depressive disorders comorbid with alcohol dependence, the effect of the 1846G> A polymorphism of the CYP2D6 gene (rs3892097) on the safety profile of mirtazapine was demonstrated, but not on the effectiveness. At the same time, hsa-miR-370-3p remains a promising biomarker for assessing the level of CYP2D6 gene expression, since the level of its plasma concentration differed in carriers of different genotypes for the polymorphic marker 1846G> A, although no connection with clinical efficacy and safety was found.

Assessment of the impact of the steady state level of microRNA hsa-miR-370-3p concentration on the efficacy and safety profile of fluvoxamine in patients with depressive disorders disorder comorbid with alcohol use disorders

2020 ◽  
pp. 37-46
Author(s):  
Mikhail Zastrozhin ◽  
Valentin Skryabin ◽  
Kristina Ryzhikova ◽  
Dmitriy Sychev
Keyword(s):  
Plasma Concentration ◽  
Alcohol Use ◽  
Depressive Disorders ◽  
State Level ◽  
Polymorphic Marker ◽  
Alcohol Addiction ◽  
Efficacy And Safety ◽  
Spectrum Disorders ◽  
Using Data ◽  
The Impact

Fluvoxamine is used in therapy for patients with depressive spectrum disorders comorbid with alcohol addiction. At the same time, a large proportion of such patients do not respond properly to fluvoxamine therapy and many of them show dose-dependent adverse reactions. Previous studies have demonstrated that CYP2D6 participates in the fluvoxamine biotransformation and its activity depends on polymorphism of the encoding gene. The purpose of this study was to evaluate the effect of CYP2D6 genetic polymorphism on the efficacy and safety of fluvoxamine using data on CYP2D6 activity evaluated by the 6M-THBC/pinoline metabolic ratio, as well as data on CYP2D6 expression level obtained by measuring plasma concentration of hsa-miR-370-3p in patients with depressive disorders comorbid with alcohol use disorder. A group of 83 patients with depressive spectrum disorders comorbid with alcohol addiction demonstrated the effect of the 1846G > A polymorphism of the CYP2D6 gene (rs3892097) on the efficacy and safety of fluvoxamine. Unfortunately, hsa-miR-370-3p turned out to be not a valid marker for assessing the level of CYP2D6 expression, since its plasma concentration did not differ in carriers of different genotypes by 1846G > A polymorphic marker.

scholarly journals The Effect of Cyp2d6 Gene Polymorphism on the Efficacy and Safety of Mirtazapine in Patients with Depressive Disorders Comorbid with Alcohol

2019 ◽  
Vol 74 (3) ◽  
pp. 185-191
Author(s):  
Mikhail S. Zastrozhin ◽  
Valery V. Smirnov ◽  
Alexander S. Sorokin ◽  
Elena A. Grishina ◽  
Kristina A. Ryzhikova ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Depressive Disorder ◽  
Alcohol Dependence ◽  
Adverse Drug Reactions ◽  
Depressive Disorders ◽  
Efficacy And Safety ◽  
Drug Reactions ◽  
Cyp2d6 Gene ◽  
Safety Indicator ◽  
Tetracyclic Antidepressants

Background: Alcohol dependence is often combined with affective disorders, in particular, depressive disorder, which adversely affects the prognosis of the course of both diseases. For the treatment of a depressive disorder, drugs from the group of tetracyclic antidepressants, of which mirtazapine is a representative, are used. Therapy with mirtazapine is associated with the risk of undesirable drug reactions and pharmacoresistance. Aim: To study the effect of CYPD6 isoenzyme activity on the efficacy and safety of mirtazapine therapy in patients with depressive disorders comorbid with alcoholism. Methods: The study was conducted on 109 Russian patients with a depressive disorder, comorbid with alcohol dependence. For the correction of depressive disorders within the framework of cyclothymia, mirtazapine was prescribed to patients at a dosage of 1545 mg/day. CYP2D6*4 genotyping (1846G A, rs3892097) was carried out using Real-time polymerase chain reaction with allele-specific hybridization. Efficacy and safety were assessed using validated psychometric scales and an assessment of the severity of adverse drug reactions. Results: By the 9th day of the study, the severity of depressive symptoms on the HAMD scale was significantly different in patients with different genotypes: (GG) 7.0 [6.0; 8.0], (GA) 4.0 [3.8; 5.0] (p0.001), safety indicator, estimated on a UKU scale: (GG) 3.0 [3.0; 3.0], (GA) 4.0 [4.0; 5.0] (p0.001). The presence of differences persisted on the 16th day: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [0.8; 3.2] (p0.001), safety indicator, estimated on a UKU scale: (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p0.001). Conclusion: In this study, the effect of CYP2D6 gene polymorphism on the efficacy and safety of therapy with mirtazapine was demonstrated. Carrying a minor allele A is associated with an increased risk of adverse drug reactions, but improving performance profile performance.

Effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder

2019 ◽  
Vol 97 (8) ◽  
pp. 781-785 ◽  
Author(s):  
M.S. Zastrozhin ◽  
V.Y. Skryabin ◽  
V.V. Smirnov ◽  
E.A. Grishina ◽  
K.A. Ryzhikova ◽  
...  
Keyword(s):  
Alcohol Use ◽  
High Performance ◽  
Alcohol Use Disorder ◽  
Depressive Disorders ◽  
Rating Scale ◽  
Correlation Coefficients ◽  
Inverse Correlation ◽  
Efficacy And Safety ◽  
Cyp2d6 Activity ◽  
Scale Scores

The objective of the study was to investigate the effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder who received mirtazapine. The study included 109 Russian patients who received mirtazapine at a dose of 30.0 [15.0; 45.0] mg per day. Genotyping of CYP2D6*4 (1846G > A, rs3892097) was performed using real-time polymerase chain reaction with allele-specific hybridization. The activity of CYP2D6 was evaluated by determining the concentration of endogenous substrate of the enzyme and its urinary metabolite — pinoline to 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline ratio, using high-performance liquid chromatography – mass spectrometry. The statistically significant differences between the scores on the Hamilton Depression Rating Scale (HAMD) in patients with different genotypes were revealed by day 16: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.2] (p < 0.001), and for the The UKU Side Effects Rating Scale (UKU): (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p < 0.001). The calculation of correlation coefficients between the differences in scale scores and metabolic rate showed the presence of statistically significant weak inverse correlation with the efficacy indicator evaluated by HAMD (r = −0.278, p < 0.05), but not by UKU (r = 0.274, p > 0.05). This study demonstrated that an increased CYP2D6 activity reduces the efficacy of treatment with mirtazapine.

scholarly journals Clinical Efficacy and Safety Profile of Prucalopride in Chronic Idiopathic Constipation

Cureus ◽  
2019 ◽  
Author(s):  
Asim Tameez Ud Din ◽  
Ameer H Khan ◽  
Hamza Bajwa ◽  
Muhammad Haisum Maqsood ◽  
Mustafa N Malik
Keyword(s):  
Clinical Efficacy ◽  
Safety Profile ◽  
Efficacy And Safety ◽  
Idiopathic Constipation ◽  
Chronic Idiopathic Constipation

Clinical efficacy and safety following dose tapering of ciclosporin in cats with hypersensitivity dermatitis

2016 ◽  
Vol 18 (11) ◽  
pp. 898-905 ◽  
Author(s):  
Elizabeth S Roberts ◽  
Tiffany Tapp ◽  
Ann Trimmer ◽  
Linda Roycroft ◽  
Stephen King
Keyword(s):  
Adverse Events ◽  
Clinical Response ◽  
Clinical Efficacy ◽  
Safety Profile ◽  
Therapeutic Response ◽  
Clinical Pathology ◽  
Efficacy And Safety ◽  
Dosing Frequency ◽  
Dosing Regimens ◽  
Physical Examinations

Objectives This study was designed to evaluate the efficacy and safety of reducing ciclosporin (CsA) dosing frequency from daily to every other day (EOD) or twice a week (TW) according to clinical response in cats with hypersensitivity dermatitis (HD) and treated with CsA. Methods One hundred and ninety-one cats with HD were given 7 mg/kg CsA daily for at least 4 weeks. Depending on clinical response, the dosing frequency was tapered from daily to EOD over the next 4 weeks and further to TW for an additional 4 weeks. Safety was evaluated through physical examinations, clinical pathology and the monitoring of adverse events (AEs). Results The majority of cats were able to have their dose of CsA tapered to either EOD (15.5%) or TW (62.9%) according to the clinical response. Observed AEs were most frequently mild and self-limiting vomiting and diarrhea. A higher percentage of AEs occurred with daily administration (73%) compared with other dosing regimens (27%). Conclusions and relevance Following 4 weeks of daily dosing at 7 mg/kg, CsA may be tapered to EOD or TW while maintaining the desired therapeutic response in cats with HD. Additionally, CsA appears to be well tolerated with fewer AEs at EOD or TW dosing. Establishing the lowest effective dosing frequency of CsA improves the drug’s safety profile.

scholarly journals A RANDOMIZED ACTIVE CONTROLLED CLINICAL STUDY TO EVALUATE EFFICACY AND SAFETY OF RESVERATROL AS AN ADJUVANT THERAPY IN PATIENTS WITH HYPERTENSION

2016 ◽  
Vol 10 (1) ◽  
pp. 376
Author(s):  
Rakesh Ojha ◽  
Kulkarni Pranesh ◽  
Vyas Bhavin
Keyword(s):  
Essential Hypertension ◽  
Adjuvant Therapy ◽  
Clinical Efficacy ◽  
Safety Profile ◽  
Gold Standard ◽  
Standard Therapy ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Hypertensive Patients

ABSTRACTObjectives: No long-term clinical efficacy and safety study of resveratrol as adjuvant therapy along with gold standard therapy has been conductedin patients with essential hypertension. The aim of this study was to investigate the efficacy and safety of resveratrol as an adjuvant therapy in newlydiagnosed hypertensive patients.Methods: In this randomized active-controlled study, hypertensive patients (male/female) of 20-65 years aged were randomized (1:1) to receivetelmisartan 20 mg or telmisartan 20 mg plus resveratrol 1 g daily for 12 months. Efficacy variables included a change in systolic and diastolic bloodpressure (DBP) from baseline and were followed up for every 3 months. Treatment-emergent adverse events were assessed.Results: A total of 60 hypertensive patients were analyzed (telmisartan [n=30] and telmisartan plus resveratrol [n=30]). Resveratrol as an adjuvantwith telmisartan significantly reduced in systolic (p<0.001) and DBP (p<0.001) as compared to telmisartan monotherapy. Change in systolic and DBPfrom baseline was significantly higher in telmisartan plus resveratrol group than telmisartan (p<0.001) at all followed visits. Both the study drugshave similar safety profile and found well tolerable.Conclusions: Resveratrol plus Telmisartan was found to be superior over telmisartan monotherapy in reducing systolic and DBP in newly diagnosedhypertensive patients. Both the study drugs were effective with comparable safety profile. Our study supports the long-term clinical efficacy andsafety study of resveratrol along with gold standard therapy in essential hypertension.Keywords: Essential hypertension, Resveratrol, Systolic and diastolic blood pressure, Telmisartan.

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