. 2022 Sep;29(5):469-480.

doi: 10.1007/s40292-022-00536-3. Epub 2022 Aug 12.

The Influence of ABCB1 (rs1045642 and rs4148738) Gene Polymorphisms on Rivaroxaban Pharmacokinetics in Patients Aged 80 Years and Older with Nonvalvular Atrial Fibrillation

Dmitry Sychev¹, Olga Ostroumova^{1

2}, Marina Cherniaeva^{3

4}, Nataliia Shakhgildian⁵, Karin Mirzaev^{1

6

7}, Sherzod Abdullaev^{1

8}, Natalia Denisenko^{1

7}, Zhannet Sozaeva^{1

7}, Anastasia Kachanova^{1

8}, Svetlana Gorbatenkova⁹, Vera Shastina⁹

Affiliations

¹ Department of Clinical Pharmacology and Therapy, Russian Medical Academy of Continuous Professional Education, 2/1 Barrikadnaya St., Moscow, 123242, Russian Federation.
² Department of Therapy and Polymorbid Pathology, Russian Medical Academy of Continuous Professional Education, 2/1 Barrikadnaya St., Moscow, 123242, Russian Federation.
³ Department of Internal and Preventive Medicine, Central State Medical Academy of the Presidential Administration of the Russian Federation, Marshal Timoshenko Street, 19, Building 1A, Moscow, 121359, Russian Federation. doctor@cherniaeva.ru.
⁴ State Budgetary Institution of Health "Hospital for War Veterans No. 2" of the Department of Health of Moscow, Volgogradskiy Prospekt, 168, Moscow, 109472, Russian Federation. doctor@cherniaeva.ru.
⁵ Lomonosov Moscow State University Medical Research and Educational Center, 27\10, Lomonosovskiy Prospekt, Moscow, 119991, Russian Federation.
⁶ Research Center for Medical Genetics, 1 Moskvorechye st., Moscow, 115522, Russian Federation.
⁷ Department of Personalized Medicine, Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education, 7/2 2nd Bokinskiy Drive, Moscow, 125284, Russian Federation.
⁸ Department of Molecular Medicine, Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education, 7/2 2nd Bokinskiy Drive, Moscow, 125284, Russian Federation.
⁹ State Budgetary Institution of Health "Hospital for War Veterans No. 2" of the Department of Health of Moscow, Volgogradskiy Prospekt, 168, Moscow, 109472, Russian Federation.

PMID: 35960493
DOI: 10.1007/s40292-022-00536-3

The Influence of ABCB1 (rs1045642 and rs4148738) Gene Polymorphisms on Rivaroxaban Pharmacokinetics in Patients Aged 80 Years and Older with Nonvalvular Atrial Fibrillation

Dmitry Sychev et al. High Blood Press Cardiovasc Prev. 2022 Sep.

. 2022 Sep;29(5):469-480.

doi: 10.1007/s40292-022-00536-3. Epub 2022 Aug 12.

Authors

Affiliations

¹ Department of Clinical Pharmacology and Therapy, Russian Medical Academy of Continuous Professional Education, 2/1 Barrikadnaya St., Moscow, 123242, Russian Federation.
² Department of Therapy and Polymorbid Pathology, Russian Medical Academy of Continuous Professional Education, 2/1 Barrikadnaya St., Moscow, 123242, Russian Federation.
³ Department of Internal and Preventive Medicine, Central State Medical Academy of the Presidential Administration of the Russian Federation, Marshal Timoshenko Street, 19, Building 1A, Moscow, 121359, Russian Federation. doctor@cherniaeva.ru.
⁴ State Budgetary Institution of Health "Hospital for War Veterans No. 2" of the Department of Health of Moscow, Volgogradskiy Prospekt, 168, Moscow, 109472, Russian Federation. doctor@cherniaeva.ru.
⁵ Lomonosov Moscow State University Medical Research and Educational Center, 27\10, Lomonosovskiy Prospekt, Moscow, 119991, Russian Federation.
⁶ Research Center for Medical Genetics, 1 Moskvorechye st., Moscow, 115522, Russian Federation.
⁷ Department of Personalized Medicine, Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education, 7/2 2nd Bokinskiy Drive, Moscow, 125284, Russian Federation.
⁸ Department of Molecular Medicine, Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education, 7/2 2nd Bokinskiy Drive, Moscow, 125284, Russian Federation.
⁹ State Budgetary Institution of Health "Hospital for War Veterans No. 2" of the Department of Health of Moscow, Volgogradskiy Prospekt, 168, Moscow, 109472, Russian Federation.

PMID: 35960493
DOI: 10.1007/s40292-022-00536-3

Abstract

Introduction: ABCB1 gene polymorphisms are associated with rivaroxaban distribution changes and adverse reactions but the data are controversial.

Aim: To evaluate the influence of ABCB1 (rs1045642 and rs4148738) gene polymorphisms on rivaroxaban pharmacokinetics in patients aged 80 years and older with nonvalvular atrial fibrillation (NAF).

Methods: 128 patients aged 80 years and older (median [Me] age 87.5 [83.0-90.0] years) with NAF were included. We performed ABCB1 (rs1045642 and rs4148738) genotyping, measured the trough steady-state plasma concentration (C_min,ss) of rivaroxaban and prothrombin time (PT) and analyzed prior medical records for clinically relevant non-major bleeding (CRNMB).

Results: CC genotype carriers had no differences in C_min,ss (p > 0.05) compared with the CT and TT rs1045642 and rs4148738 genotypes carriers. CC genotype carriers had no differences in PT (p > 0.05) compared with the CT rs1045642 and rs4148738 and TT rs4148738 genotypes carriers. In the TT genotype PT levels were higher than in the CC rs1045642 genotype: Me 14.2 [13.0-16.1] sec vs 13.3 [12.4-14.5] sec (p = 0.049). Incidence of CRNMB was higher in patients with the TT genotype compared with the CC rs1045642 (29.3% vs 4.5%, p = 0.021) and rs4148738 (39.3% vs 8.1%, p = 0.008) and the CT genotype rs4148738 (39.3% vs 14.3%, p = 0.002).

Conclusion: ABCB1 (rs1045642 and rs4148738) polymorphisms didn't influence rivaroxaban pharmacokinetics in patients aged 80 years and older with NAF. TT carriers developed CRNMB more frequently compared with the CC rs1045642 and the CC and CT rs4148738 genotypes. The haplotype TT-TT haplotype was associated with a higher frequency of CRNMB.

Keywords: ABCB1 (rs1045642); ABCB1 (rs4148738); Elderly patients; Nonvalvular atrial fibrillation; Pharmacogenetics; Rivaroxaban.

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The Influence of ABCB1 (rs1045642 and rs4148738) Gene Polymorphisms on Rivaroxaban Pharmacokinetics in Patients Aged 80 Years and Older with Nonvalvular Atrial Fibrillation

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The Influence of ABCB1 (rs1045642 and rs4148738) Gene Polymorphisms on Rivaroxaban Pharmacokinetics in Patients Aged 80 Years and Older with Nonvalvular Atrial Fibrillation

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