Peculiarities of dabigatran pharmacogenetics: literature review

Рубаненко, А. О.; Rubanenko, O. A.; Shchukin, Yurii V.

doi:10.35336/va-2022-1-06

Cited by 2 publications

(1 citation statement)

References 37 publications

(55 reference statements)

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“…Based on the latest data from this pharmacogenomics database, the determination of rs2244613 and rs8192935 CES1 polymorphisms, as well as rs1045642 , rs2032582 , and rs4148738 ABCB1 polymorphisms in patients taking dabigatran has a low level (3) of evidence, which prevents us from recommending the determination of these CES1 and ABCB1 genetic polymorphisms in the routine clinical practice. 28 , 60 …”

Section: Discussionmentioning

confidence: 99%

Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulants

Abdrakhmanov,

Shaimerdinova,

Suleimen

et al. 2024

Therapeutic Advances in Cardiovascular Disease

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Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs. This review is aimed at analyzing the scientific literature on the gene polymorphisms involved in the metabolism of DOACs. We searched PubMed, Cochrane, Google Scholar, and CyberLeninka (Russian version) databases with keywords: ‘dabigatran’, ‘apixaban’, ‘rivaroxaban’, ‘edoxaban’, ‘gene polymorphism’, ‘pharmacogenetics’, ‘ ABCB1’, ‘ CES1’, ‘ SULT1A’, ‘ ABCG2’, and ‘ CYP3A4’. The articles referred for this review include (1) full-text articles; (2) study design with meta-analysis, an observational study in patients taking DOAC; and (3) data on the single-nucleotide polymorphisms and kinetic parameters of DOACs (plasma concentration), or a particular clinical outcome, published in English and Russian languages during the last 10 years. The ages of the patients ranged from 18 to 75 years. Out of 114 reviewed works, 24 were found eligible. As per the available pharmacogenomic data, polymorphisms affecting DOACs are different. This may aid in developing individual approaches to optimize DOAC pharmacotherapy to reduce the risk of hemorrhagic complications. However, large-scale population studies are required to determine the dosage of the new oral anticoagulants based on genotyping. Information on the genetic effects is limited owing to the lack of large-scale studies. Uncovering the mechanisms of the genetic basis of sensitivity to DOACs helps in developing personalized therapy based on patient-specific genetic variants and improves the efficacy and safety of DOACs in the general population.

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Section: Discussionmentioning

confidence: 99%

Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulants

Abdrakhmanov,

Shaimerdinova,

Suleimen

et al. 2024

Therapeutic Advances in Cardiovascular Disease

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Pharmacokinetics and bioequivalence of the generic and original dabigatran etexilate after a single dose in healthy volunteers

Vasilyuk,

Faraponova,

Verveda

et al. 2024

Russ J Cardiol

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Aim. To study the comparative pharmacokinetics and confirmation of bioequivalence of the generic (T) and original (R) dabigatran etexilate in healthy volunteers after a single oral dose under fasted conditions.Material and methods. To confirm bioequivalence, an open-label, randomized, replication, crossover, four-step study was conducted to compare the pharmacokinetics and bioequivalence of generic and original dabigatran with a single oral dose 150 mg dabigatran etexilate under fasted conditions in adult healthy male and female volunteers. Sixty-eight subjects participated in the study. During the study, blood plasma samples were taken from volunteers, in which the concentration of total and free dabigatran was determined. Based on the data obtained, pharmacokinetic and statistical analysis was carried out and 90% confidence intervals were calculated for the ratio of mean pharmacokinetic parameters (Сmax, Tmax, AUC0-t, AUC0-∞, AUCt-∞, T1/2, AUCt-∞/AUC0-∞) for total and free dabigatran.Results. The established 90% confidence intervals for the ratio of AUC0-t, AUC0-∞ and Cmax values for total dabigatran were 82,56-96,36% (mean ratio, 89,19%), 82,39-95,90% (mean ratio, 88,89%) and 85,98-99,17% (mean ratio, 92,34%), respectively. The established 90% confidence intervals for the ratio of AUC0-t, AUC0-∞ and Сmax values for free dabigatran were 83,37-98,29% (mean ratio, 90,53%), 82,98-97,33% (mean ratio, 89,87%) and 85,04-99,28% (mean ratio, 91,88%), respectively. For the estimated pharmacokinetic parameters of dabigatran etexilate, 90% confidence intervals ranged from 80-125% for AUC0-t, AUC0-∞ and Cmax. Additional safety analysis was carried out. Generic and original dabigatran were well tolerated by the volunteers. There were no significant differences in vital signs, paraclinical characteristics throughout the study compared with the initial data, as well as significant differences between the drugs in all studied parameters of adverse events.Conclusion. The study showed that generic and original dabigatran are bioequivalent. In addition, the data obtained indicate that the agents have similar safety profiles.

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Peculiarities of dabigatran pharmacogenetics: literature review

Cited by 2 publications

References 37 publications

Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulants

Gene polymorphism as a cause of hemorrhagic complications in patients with non-valvular atrial fibrillation treated with oral vitamin K-independent anticoagulants

Pharmacokinetics and bioequivalence of the generic and original dabigatran etexilate after a single dose in healthy volunteers

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