Pharmacogenetics of Direct Oral Anticoagulants

Shnayder, N. А.; Петрова, М. М.; Bochanova, E. N.; Zimnitskaya, O. V.; Savinova, A. V.; Пожиленкова, Е. А.; Насырова, Р. Ф.

doi:10.5772/intechopen.95966

Cited by 8 publications

(1 citation statement)

References 98 publications

(107 reference statements)

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“…problems and, accordingly, lead to additional financial costs associated with ineffective treatment, the development of complications and the need to prescribe other medications or methods of therapy for both the treatment of the underlying disease and the correction of ADRs [4,5] . The metabolism of AEDs can be influenced by polymorphism of the genes CYP2C9, CYP2C19, CYP3A4 of the liver cytochrome P450 isoenzymes [6]. However, a personalized approach to the prevention of HP in patients with epilepsy, taking into account individual pharmacogenetic characteristics, has been implemented only in certain regions of the Russia [7,8].…”

Section: Introductionmentioning

confidence: 99%

The Frequency and Structure of Adverse Drug Reactions in the Pharmacotherapy of Epilepsy

Bochanova,

Gusev

2024

jour

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The problem of the safety of antiepileptic therapy due to the duration of treatment and the need for regular intake of antiepileptic drugs (AEDs) is extremely significant. Adverse reactions (ADRs) may outweigh any positive effect of therapy associated with seizure reduction. The purpose of the study: to analyze the frequency and structure of ADRs of AEDs. Materials and Methods: The work was carried out within the framework of comprehensive research on the topic No. 210-16 "Epidemiological, genetic and neurophysiological aspects of diseases of the nervous system (central, peripheral and vegetative) and preventive medicine" (registration number 0120.0807480). Results: The frequency of ADRs against the background of third-generation AEDs was not inferior to that against the background of receiving second-generation AEDs, while the structure of ADRs was different: third-generation AEDs had a higher incidence of ADRs from the central nervous system, including a worsening of the course of epilepsy. The ratio of the chances of valproic acid accumulation with the achievement of toxic concentration in the blood and the development of un-desirable side effects in poor metabolizers (carriers of the polymorphism of CYP2C9*2 or CYP2C9*3) the gene encoding the cytochrome P450 isoenzyme 2C9 of the liver is 5.94 and 4.27, respectively. Conclusion: A personalized approach to ensuring the safety of valproic acid preparations based on taking into account the carriage of polymorphisms of the CYP2C9 gene allows to reduce the incidence of ADRs in patients receiving valproic acid preparations from 59.28% to 10.78%. The introduction of a personalized approach to the administration of valproates to patients suffering from epilepsy in the Krasnoyarsk Territory did not lead to an increase in direct costs.

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Section: Introductionmentioning

confidence: 99%

The Frequency and Structure of Adverse Drug Reactions in the Pharmacotherapy of Epilepsy

Bochanova,

Gusev

2024

jour

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Circulating miR-320a-3p and miR-483-5p level associated with pharmacokinetic–pharmacodynamic profiles of rivaroxaban

Zhang

Liu

et al. 2022

Hum Genomics

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Background Novel biomarkers for personalizing anticoagulation remain undetermined. We aimed to investigate the association of plasma miRNAs with pharmacokinetic–pharmacodynamic (PK-PD) profiles of rivaroxaban. Methods This is a multicenter, exploratory study of miRNAs in a Chinese population. Healthy volunteers and patients receiving rivaroxaban were enrolled in the study. The area under the plasma concentration–time curve from time 0-t h (AUC0-t) and anti-Xa activity at 3 h (AXA3h) were measured in healthy volunteers, and AXA3h was measured in patients. MiRNAs were detected by miRNA microarray in 26 healthy volunteers with 20 mg rivaroxaban, and quantitative reverse transcription polymerase chain reaction was used to exclude undetectable ones. MiR-320a-3p and miR-483-5p were then quantified in 65 healthy volunteers and 71 patients. MiRNA levels at 3 h were compared between high and low AXA3h or AUC0-t subjects and in matched patients with or without bleeding during follow-up. The miRNA targets were predicted by TargetScan, miRTarBase, and miRDB. Validated genes were included in GO enrichment and KEGG analyses. The protein–protein interaction network was established by STRING and visualized by Cytoscape. Results A total of 136 Chinese subjects completed the study. In healthy volunteers taking 15 mg rivaroxaban, the miR-320a level at 3 h was significantly positively correlated with AXA3h and AUC0-t (r = 0.359, p = 0.025; r = 0.370, p = 0.02, respectively). A positive correlation was also observed between miR-483 and AXA3h or AUC0-t (r = 0.372, p = 0.02; r = 0.523, p = 0.001, respectively). MiR-320a and miR-483 levels at 3 h in the higher AUC0-t group were significantly higher than those at 0 h. MiR-483 levels at 3 h may distinguish healthy volunteers with high or low AXA3h or AUC0-t. In the 10 mg fed subgroup, higher 3 h mir-483 levels were also observed compared with the control group. No significant differences were found in the comparisons among patients. Bioinformatic analysis showed that these miRNAs may play a regulatory role by targeting ABCG2, ITGB3, PTEN, MAPK1/3, etc. Conclusions MiR-320a and miR-483 levels were found to be associated with PK and PD profiles of rivaroxaban in healthy Chinese subjects. Further studies are required to verify these findings and explore the mechanisms.

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Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment

Shnayder

Ashkhotov

Trefilova³

et al. 2023

IJMS

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Intervertebral disc degeneration (IDD) and associated conditions are an important problem in modern medicine. The onset of IDD may be in childhood and adolescence in patients with a genetic predisposition. With age, IDD progresses, leading to spondylosis, spondylarthrosis, herniated disc, spinal canal stenosis. One of the leading mechanisms in the development of IDD and chronic back pain is an imbalance between pro-inflammatory and anti-inflammatory cytokines. However, classical therapeutic strategies for correcting cytokine imbalance in IDD do not give the expected response in more than half of the cases. The purpose of this review is to update knowledge about new and promising therapeutic strategies based on the correction of the molecular mechanisms of cytokine imbalance in patients with IDD. This review demonstrates that knowledge of the molecular mechanisms of the imbalance between pro-inflammatory and anti-inflammatory cytokines may be a new key to finding more effective drugs for the treatment of IDD in the setting of acute and chronic inflammation.

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Pharmacogenetics of Direct Oral Anticoagulants

Cited by 8 publications

References 98 publications

The Frequency and Structure of Adverse Drug Reactions in the Pharmacotherapy of Epilepsy

The Frequency and Structure of Adverse Drug Reactions in the Pharmacotherapy of Epilepsy

Circulating miR-320a-3p and miR-483-5p level associated with pharmacokinetic–pharmacodynamic profiles of rivaroxaban

Molecular Basic of Pharmacotherapy of Cytokine Imbalance as a Component of Intervertebral Disc Degeneration Treatment

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