Aims: Dabigatran is largely cleared by renal excretion. Renal function is thus a major determinant of trough dabigatran concentrations, which correlate with the risk of thromboembolic and haemorrhagic outcomes. Current dabigatran dosing guidelines use the Cockcroft-Gault (CG) equation to gauge renal function, instead of contemporary equations including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations employing creatinine (CKD-EPI_Cr), cystatin C (CKD-EPI_Cys) and both renal biomarkers (CKD-EPI_CrCys).
Methods: A linear regression model including the dabigatran etexilate maintenance dose rate, relevant interacting drugs and genetic polymorphisms (including CES1), was used to analyse the relationship between the values from each renal function equation and trough steady-state plasma dabigatran concentrations.
Results: The median dose-corrected trough steady-state plasma dabigatran concentration in 52 patients (38-94 years) taking dabigatran etexilate was 60 µg/L (range 9-279). The dose-corrected trough concentration in a patient on phenytoin and phenobarbitone was >3 standard deviations below the cohort mean. The CG, CKD-EPI_Cr, CKD-EPI_Cys and CKD-EPI_CrCys equations explained (R (2), 95 % CI) 32 % (9-55), 37 % (12-60), 41 % (16-64) and 47 % (20-69) of the variability in dabigatran concentrations between patients, respectively. One-way analysis of variance (ANOVA) comparing the R (2) values for each equation was not statistically significant (p = 0.74).
Discussion: Estimates of renal function using the four equations accounted for 32-47 % of the variability in dabigatran concentrations between patients. We are the first to provide evidence that co-administration of phenytoin/phenobarbitone with dabigatran etexilate is associated with significantly reduced dabigatran exposure.
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http://dx.doi.org/10.1007/s40268-014-0045-9 | DOI Listing |
J Thromb Thrombolysis
December 2024
Melbourne Dental School, The University of Melbourne Melbourne Dental School, Victoria, Australia.
Animal models of thrombosis play a critical role in research, helping us understand the mechanisms of hemostasis and thrombus formation, as well as in the screening of anti-thrombotic drugs. This study aimed to evaluate the safety profile of two anticoagulants in murine research and to assess coagulation parameters, including prothrombin time (PT) and activated partial thromboplastin time (aPTT), using the VETSCAN VSpro coagulation analyzer in wild-type (C57BL/6) mice following administration of anticoagulants. Two experiments were conducted involving a total of sixty wild-type mice that received two common anticoagulants.
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December 2024
Department of Neurosciences, Bufalini Hospital, AUSL Romagna, Viale Ghirotti 286, 47521, Cesena, Italy.
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Scand J Clin Lab Invest
December 2024
The Medical Faculty, Lund University Sweden. Sölveg, Lund, Sweden.
Direct oral anticoagulants (DOAC) are increasingly common, with bleeding events associated with elevated plasma concentrations. Rotational thromboelastometry (ROTEM), a point-of-care tool for assessing secondary hemostasis, has demonstrated a correlation with increasing concentrations of DOAC. However, previous studies have only partially explored this relationship.
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November 2024
Clinical Trials Center, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Diagnostics (Basel)
November 2024
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122 Milano, Italy.
. Alterations induced by direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) to thromboelastometry and thrombin generation are not well defined. We performed a simultaneous investigation of thromboelastometry and thrombin generation for patients who were chronically anticoagulated with DOACs or VKAs.
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