Effect of CES1 and ABCB1 genotypes on the pharmacokinetics and clinical outcomes of dabigatran etexilate in patients with atrial fibrillation and chronic kidney disease.

Drug Metabolism and Personalized Therapy
Dmitriy A SychevViktor Fomin

Abstract

Background Despite the well-studied safety profile of dabigatran, its interactions with genetic polymorphism parameters are poorly understood, especially in patients with moderate chronic kidney disease (CKD). The study assessed whether genetic factors can contribute to CKD and alter dabigatran concentration. Methods Patients with atrial fibrillation (AF) and stage 3 CKD treated with dabigatran 110 or 150 mg have been included in the study. Real-time polymerase chain reaction was used to evaluate single-nucleotide polymorphisms of the ABCB1 gene (rs1045642 and rs4148738) and CES1 gene (rs2244613). A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index. Results A total of 96 patients aged 51-89 years (median age: 75 years) were evaluated. Patients on a reduced regimen of 110 mg twice a day were older (79.8 vs. 67.9, p < 0.0001) and had lower creatinine clearance (49.7 vs. 62.3 mL/min/1.73 m2, p = 0.015). Patients with the rs2244613 CC genotype had lower C/D values (70% reduction in the mean C/D vs. AA genotype, p = 0.001). Linear stepwise regression has shown the CKD epidemiology collaboration to be the only significant predictor of C/D among genetic factors and kidney function characteristics. During...Continue Reading

References

Apr 29, 1982·The New England Journal of Medicine·W B KannelP M McNamara
Mar 8, 2013·Circulation·Guillaume ParéLars Wallentin
Dec 19, 2013·Circulation·Sumeet S ChughChristopher J L Murray
Jun 5, 2016·Thrombosis Research·Claudia DimatteoMaurizio Margaglione
Nov 4, 2016·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Paulus KirchhofKatja Zeppenfeld

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Citations

May 28, 2021·Clinical Pharmacology and Therapeutics·Jaakko LähteenmäkiMark van Gils

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