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The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty

BACKGROUND: Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is on...

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Autores principales: Sychev, Dmitriy Alekseevich, Levanov, Alexander Nikolaevich, Shelekhova, Tatiana Vladimirovna, Bochkov, Pavel Olegovich, Denisenko, Natalia Pavlovna, Ryzhikova, Kristina Anatolyevna, Mirzaev, Karin Badavievich, Grishina, Elena Anatolyevna, Gavrilov, Mikhail Alekseevich, Ramenskaya, Galina Vladislavovna, Kozlov, Aleksei Vladimirovich, Bogoslovsky, Tanya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064159/
https://www.ncbi.nlm.nih.gov/pubmed/30100750
http://dx.doi.org/10.2147/PGPM.S169277
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author Sychev, Dmitriy Alekseevich
Levanov, Alexander Nikolaevich
Shelekhova, Tatiana Vladimirovna
Bochkov, Pavel Olegovich
Denisenko, Natalia Pavlovna
Ryzhikova, Kristina Anatolyevna
Mirzaev, Karin Badavievich
Grishina, Elena Anatolyevna
Gavrilov, Mikhail Alekseevich
Ramenskaya, Galina Vladislavovna
Kozlov, Aleksei Vladimirovich
Bogoslovsky, Tanya
author_facet Sychev, Dmitriy Alekseevich
Levanov, Alexander Nikolaevich
Shelekhova, Tatiana Vladimirovna
Bochkov, Pavel Olegovich
Denisenko, Natalia Pavlovna
Ryzhikova, Kristina Anatolyevna
Mirzaev, Karin Badavievich
Grishina, Elena Anatolyevna
Gavrilov, Mikhail Alekseevich
Ramenskaya, Galina Vladislavovna
Kozlov, Aleksei Vladimirovich
Bogoslovsky, Tanya
author_sort Sychev, Dmitriy Alekseevich
collection PubMed
description BACKGROUND: Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is one of the most commonly prescribed direct thrombin inhibitors for the prevention of VTE. The objectives of this study were to assess the effect of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) polymorphisms on dabigatran pharmacokinetics in patients after total knee arthroplasty. PATIENTS AND METHODS: A total of 60 patients, aged 37–81 years, who underwent surgery for knee replacement have been included in the study. VTE prophylaxis was conducted via administration of dabigatran etexilate 220 mg once daily. Genotyping for carrier state of polymorphic variants such as rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene was carried out using real-time polymerase chain reaction (PCR). We also measured the peak and trough concentrations of plasma dabigatran by using high-performance liquid chromatography (HPLC). RESULTS: Our study revealed that TT genotype of rs1045642 polymorphism of the ABCB1 gene was associated with higher dabigatran equilibrium peak concentrations and the higher risk of bleeding than the presence of CC genotype (p<0.008). There was no statistically significant genotype-dependent difference in the trough concentrations between rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene. CONCLUSION: Our findings indicate that the polymorphisms of ABCB1 rs1045642 may have a prominent contribution to the safety of dabigatran in patients after knee surgery. Moreover, TT genotype may be associated with the higher risk of hemorrhagic complications in this population. There were no influence of polymorphism of ABCB1 rs4148738 and CES1 rs2244613 on dabigatran peak and through concentrations. Larger studies are needed to confirm our observations.
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spelling pubmed-60641592018-08-10 The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty Sychev, Dmitriy Alekseevich Levanov, Alexander Nikolaevich Shelekhova, Tatiana Vladimirovna Bochkov, Pavel Olegovich Denisenko, Natalia Pavlovna Ryzhikova, Kristina Anatolyevna Mirzaev, Karin Badavievich Grishina, Elena Anatolyevna Gavrilov, Mikhail Alekseevich Ramenskaya, Galina Vladislavovna Kozlov, Aleksei Vladimirovich Bogoslovsky, Tanya Pharmgenomics Pers Med Original Research BACKGROUND: Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is one of the most commonly prescribed direct thrombin inhibitors for the prevention of VTE. The objectives of this study were to assess the effect of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) polymorphisms on dabigatran pharmacokinetics in patients after total knee arthroplasty. PATIENTS AND METHODS: A total of 60 patients, aged 37–81 years, who underwent surgery for knee replacement have been included in the study. VTE prophylaxis was conducted via administration of dabigatran etexilate 220 mg once daily. Genotyping for carrier state of polymorphic variants such as rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene was carried out using real-time polymerase chain reaction (PCR). We also measured the peak and trough concentrations of plasma dabigatran by using high-performance liquid chromatography (HPLC). RESULTS: Our study revealed that TT genotype of rs1045642 polymorphism of the ABCB1 gene was associated with higher dabigatran equilibrium peak concentrations and the higher risk of bleeding than the presence of CC genotype (p<0.008). There was no statistically significant genotype-dependent difference in the trough concentrations between rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene. CONCLUSION: Our findings indicate that the polymorphisms of ABCB1 rs1045642 may have a prominent contribution to the safety of dabigatran in patients after knee surgery. Moreover, TT genotype may be associated with the higher risk of hemorrhagic complications in this population. There were no influence of polymorphism of ABCB1 rs4148738 and CES1 rs2244613 on dabigatran peak and through concentrations. Larger studies are needed to confirm our observations. Dove Medical Press 2018-07-25 /pmc/articles/PMC6064159/ /pubmed/30100750 http://dx.doi.org/10.2147/PGPM.S169277 Text en © 2018 Sychev et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Sychev, Dmitriy Alekseevich
Levanov, Alexander Nikolaevich
Shelekhova, Tatiana Vladimirovna
Bochkov, Pavel Olegovich
Denisenko, Natalia Pavlovna
Ryzhikova, Kristina Anatolyevna
Mirzaev, Karin Badavievich
Grishina, Elena Anatolyevna
Gavrilov, Mikhail Alekseevich
Ramenskaya, Galina Vladislavovna
Kozlov, Aleksei Vladimirovich
Bogoslovsky, Tanya
The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty
title The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty
title_full The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty
title_fullStr The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty
title_full_unstemmed The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty
title_short The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty
title_sort impact of abcb1 (rs1045642 and rs4148738) and ces1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064159/
https://www.ncbi.nlm.nih.gov/pubmed/30100750
http://dx.doi.org/10.2147/PGPM.S169277
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