2022 December 14
PGX2’s algorithm is unparalleled with sources from US and international institutions and clinician approval validated by KOL
PGX2’s algorithm is unparalleled with sources from US and international institutions and clinician approval validated by KOL
Dr. Grace Cheney

Abstract

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2021 February 19
https://www.nature.com/articles/s41397-021-00219-7
Effects of CYP2C19 genetic polymorphism on the steady-state concentration of citalopram in patients with major depressive disorder
M S Zastrozhin,V Yu Skryabin,etc

Abstract

Citalopram 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.

2020 September 01
https://doi.org/10.1515/dmpt-2019-0033
Using a pharmacogenetic clinical decision support system to improve psychopharmacotherapy dosing in patients with affective disorders
M S Zastrozhin,V Yu Skryabin,etc

Abstract

Although pharmacogenetic tests provide the information on a genotype and the predicted phenotype, these tests do not themselves provide the interpretation of data for a physician. Currently, there are approximately two dozen pharmacogenomic clinical decision support systems (CDSSs) used in psychiatry. Implementation of the CDSSs forming the recommendations on drug and dose selection according to the results of pharmacogenetic testing is an urgent task. Fulfillment of this task will allow increasing the efficacy of therapy and decreasing the risk of undesirable side effects.

2020 May 20
doi: 10.1016/j.gene.2020.144513. Epub2020 Feb 26.
Effects of plasma concentration of micro-RNA Mir-27b and CYP3A4*22 on equilibrium concentration of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder
M S Zastrozhin,V Yu Skryabin,etc

Abstract

Alprazolam is used in the treatment of patients with anxiety disorders comorbid with alcohol use disorder. Some proportion of these patients does not respond adequately to treatment with alprazolam, while many of them experience dose-dependent adverse drug reactions. Results of the previous studies have shown that CYP3A is involved in the biotransformation of alprazolam, the activity of which is dependent, inter alia, on the polymorphism of the encoding gene.

2020 April 27
https://www.futuremedicine.com/doi/abs/10.2217/pgs-2019-0071?journalCode=pgs&
CYP3A subfamily activity affects the equilibrium concentration of Phenazepam® in patients with anxiety disorders and comorbid alcohol use disorder
M S Zastrozhin,V Yu Skryabin,etc

Abstract

Phenazepam®is prescribed to relieve anxiety and sleep disorders during alcohol withdrawal, although it is associated with undesirable side effects. Aim:To demonstrate changes in the safety and efficacy profiles of Phenazepamin patients with anxiety disorders and comorbid alcohol use disorder. Materials & methods:A total of 94 Russian patients with alcohol use disorder received 4.0mg of Phenazepamper day in tablets. We used a urinary 6-beta-hydroxycortisol/cortisol ratio to evaluate CYP3A activity. Results:A statistically significant inverse correlation between Phenazepamplasma concentration and CYP3A activity was found (r=-0.340 and p=0.017). Correlation between the concentration/dose ratio and phenotyping results was also statistically significant (r=0.301 and p=0.026). Conclusion:The safety and efficacy of Phenazepamdepend on CYP3A genetic polymorphisms.

2020 Mar 05
https://www.degruyter.com/view/journals/dmdi/35/1/article-20190026.xml
How do CYP2C19*2 and CYP2C19*17 genetic polymorphisms affect the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome?
M S Zastrozhin,V Yu Skryabin, M. V. Torrado , E. A. Grishinaetc

Abstract

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.

2020 May 20
https://www.dovepress.com/front_end/cr_data/cache/pdf/download_1591089252_5ed618646b34e/pgpm-160763-effects-of-cyp2d6-genetic-polymorphisms-on-the-efficacy-and--062818.pdf
Effects of plasma concentration of micro-RNA Mir-27b and CYP3A4*22 on equilibrium concentration of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder
M S Zastrozhin,V Yu Skryabin,etc

Abstract

Alprazolam is used in the treatment of patients with anxiety disorders comorbid with alcohol use disorder. Some proportion of these patients does not respond adequately to treatment with alprazolam, while many of them experience dose-dependent adverse drug reactions. Results of the previous studies have shown that CYP3A is involved in the biotransformation of alprazolam, the activity of which is dependent, inter alia, on the polymorphism of the encoding gene.

2020 May 20
https://doi.org/10.1139/cjpp-2019-0177
Effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder
M S Zastrozhin,V Yu Skryabin,etc

Abstract

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.

2020 Jan 20
https://doi.org/10.2217/pgs-2019-0019
Effects of CYP2C19*2 polymorphisms on the efficacy and safety of phenazepam in patients with anxiety disorder and comorbid alcohol use disorder
M S Zastrozhin,V Yu Skryabin,etc

Abstract

Introduction: Phenazepam therapy can often be ineffective and some patients develop dose-related adverse drug reactions. Aim. The purpose of this research was to study the effect of the CYP2C19*2 (681G>A, rs4244285) in patients with anxiety disorders and alcohol dependence taking phenazepam therapy. Materials & methods: Patients (175 males, average age: 37.16 ± 7.84 years) received phenazepam in tablet form for 5 days. Genotyping was performed by real-time polymerase chain reaction. Results: The statistically significant differences in the UKU Side-Effect Rating Scale scores on the fifth day of therapy: (CYP2C19*1/*1) 2.00 [1.00; 2.00), (CYP2C19*1/*2) 7.00 (7.00; 7.00), (CYP2C19*2/*2) 9.00 (8.00; 9.00), p < 0.001. Conclusion: This study demonstrated the different efficacy and safety of phenazepam in patients with different genotypes of CYP2C19*2.