Observational Study of the Inter-Individual Variability of the Plasma Concentrations of Direct Oral Anticoagulants (Dabigatran, Rivaroxaban, Apixaban) and the Effect of rs4148738 Polymorphism of ABCB1
DOI:
https://doi.org/10.12970/2311-052X.2019.07.02Keywords:
Stroke, brain lesions, aphasia, speech pathology, auditory comprehension, BDAE.Abstract
Background and Aim: Direct oral anticoagulants (DOACs, i.e dabigatran, rivaroxaban, apixaban) can be administered in fixed doses without laboratory monitoring, however pharmacokinetic and pharmacodynamic characteristics indicate that clinical, demographic and pharmacogenetic factors can influence DOAC antithrombotic efficacy. The aim of this study was to establish the inter-individual variability of DOAC plasma concentrations and influence of ABCB1 rs4148738 polymorphism on DOAC plasma levels.
Materials and Methods: Patients (n=291) taking DOACs for either venous thromboembolism (VTE) or atrial fibrillation (AF) since at least 7 days were enrolled. Demographic and clinical characteristics were collected at enrollment on a standardized form. Diluted thrombin time was measured for dabigatran and anti-Xa activity for apixaban and rivaroxaban on plasmas obtained from blood samples collected in sodium citrate after one month at trough and at peak, e.g. at 2 hours after the morning dose. DNA was extracted from peripheral leukocytes for detection of rs4148738 ABCB1 – P-glycoprotein (P-gp) (intronic region G>A) polymorphism.
Results: All DOACs showed a high inter-individual variability for both peak and trough concentrations in the 291 enrolled patients. Dabigatran peak and trough levels were correlated with creatinine clearance. The ABCB1 gene rs4148738 polymorphism was determined in 142 patients and it influenced peak levels of rivaroxaban 20 mg with lower levels in homozygotes for the minor A allele but not those of apixaban. A non significant effect was observed on dabigatran 150 mg bid peak and trough levels of.
Conclusions: The rs4148738 polymorphism of ABCB1 gene of P-gp can influence rivaroxaban peak and trough levels.
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