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Rational Pharmacotherapy in Cardiology

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PHARMACOGENETIC ASPECTS OF NEW ORAL ANTICOAGULANTS APPLICATION

https://doi.org/10.20996/1819-6446-2017-13-3-416-421

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Abstract

The aim of this review is to assess the effect of genetic factors on the pharmacokinetic parameters of new oral anticoagulants. The review presents data from studies investigating the effect of gene polymorphisms that encode biotransformation enzymes and transporter proteins of new oral anticoagulants on the pharmacokinetics of these drugs. RE-LY study showed a 15% decrease in trough dabigatran concentration and 27% lower risk of bleeding in carriers of CES1 gene rs2244613 polymorphism, there was also a tendency to reduce the risk of major bleeding. Further study of CES1 gene rs8192935 polymorphism showed a 3% decrease in trough dabigatran concentration in heterozygotes and 11% in homozygotes. There was found a 2% and 3% decrease in trough concentrations in hetero- and homozygotes for the minor allele of CES1 gene rs2244613 polymorphism, respectively. There was no significant effect of ABCB1 gene rs2032582 and rs1045642 polymorphisms on dabigatran pharmacokinetics. It is known the case of gastrointestinal bleeding in the carrier of allelic variants of ABCB1 gene rs2032582 and rs1045642 polymorphisms. However, there was no significant effect of genotype on rivaroxaban pharmacokinetics in the study involving the carriers of ABCB1 gene rs2032582 and rs1045642 polymorphisms. ABCB1 gene rs4148738 polymorphism was associated with higher apixaban peak concentration. But groups of patients with acute cardioembolic stroke showed no statistically significant difference of apixaban peak concentration depending on ABCB1 gene rs1045642 polymorphism genotype. ABCB1 gene rs1045642 and SLCO1B1 gene rs4149056 polymorphisms have no effect on edoxaban pharmacokinetics. Elevation of edoxaban metabolite concentration in carriers of SLCO1B1 gene allelic variants was not clinically significant because the proportion of metabolite is about 10% of the concentration of the main substance. It is necessary to provide large population studies with control of treatment efficacy and safety to prove clinical significance of genotyping for new oral anticoagulants use.

About the Authors

A. V. Kryukov
Russian Medical Academy of Continuing Professional Education
Russian Federation

Alexander V. Kryukov - MD, Post-Graduate Student, Chair of Clinical Pharmacology and Therapy 

Barrikadnaya ul. 2/1, Moscow, 123995



D. A. Sychev
Russian Medical Academy of Continuing Professional Education
Russian Federation
Dmitry A. Sychev - MD, PhD, Professor, Corresponding Member
of the Russian Academy of Sciences, Head of Chair of Clinical Pharmacology and Therapy, Russian Medical Academy of Continuing Professional Education; Leading Researcher, Group of Clinical Pharmacological Technologies, Research Centre of Russian Medical Academy of Continuing Professional Education


O. V. Tereshchenko
Pirogov Russian National Research Medical University
Russian Federation

Olesia V. Tereshchenko – Undergraduate Student, Therapeutic Faculty 

Ostrovitianova ul. 1, Moscow, 117997



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For citation:


Kryukov A.V., Sychev D.A., Tereshchenko O.V. PHARMACOGENETIC ASPECTS OF NEW ORAL ANTICOAGULANTS APPLICATION. Rational Pharmacotherapy in Cardiology. 2017;13(3):416-421. (In Russ.) https://doi.org/10.20996/1819-6446-2017-13-3-416-421

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)