Dabigatran is a highly selective, reversible, and potent thrombin inhibitor and is orally available as the prodrug, dabigatran etexilate. It has shown antithrombotic efficacy in animal models of thrombosis, with a rapid onset of action and predictable pharmacodynamic response. Peak plasma concentrations of dabigatran occur 1 to 2 hours after ingestion of the prodrug. The terminal half-life of dabigatran is 12 to 14 hours in elderly volunteers. Dabigatran is not metabolized by cytochrome P450 isoenzymes and does not interact with food. Dabigatran has a low potential for drug-drug interactions and is predominantly renally excreted. Dabigatran etexilate as chronic therapy effectively prevents the recurrence of venous thromboembolism and cardioembolic stroke. For the first time, it has been demonstrated clinically that there may be an effective and safe alternative to warfarin.
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http://dx.doi.org/10.1161/ATVBAHA.110.203604 | DOI Listing |
J Thromb Haemost
January 2025
Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
Introduction: The pediatric direct oral anticoagulation (DOAC) trials provide an opportunity to evaluate and characterize challenges in their design and execution to inform future antithrombotic trials.
Objective: To perform a systematic review of pediatric DOAC trials for the treatment of venous thromboembolism to critically appraise their methodology and understand the feasibility and challenges.
Methods: Systematic search of MEDLINE, EMBASE, the Cochrane Library and ClinicalTrials.
J Clin Med
December 2024
Department of Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan.
: Direct oral anticoagulants (DOACs) are frequently used to prevent embolism in atrial fibrillation. Gastrointestinal bleeding is frequent, but its drug-specific characteristics remain unclear. This study examined the frequency and characteristics of gastrointestinal bleeding in patients with nonvalvular atrial fibrillation for different DOACs.
View Article and Find Full Text PDFClin Pharmacol Ther
January 2025
Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
OATP1B, P-gp, BCRP, and CYP3A are the most contributing drug-metabolizing enzymes or transporters (DMETs) for commonly prescribed medication. Their activities may change in end-stage renal disease (ESRD) patients with large inter-individual variabilities (IIVs), leading to altered substrate drug exposure and ultimately elevated safety risk. However, the changing extent and indictive influencing factors are not quantified so far.
View Article and Find Full Text PDFBMJ Open
January 2025
School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia
Objective: To evaluate the relationship between infarct pattern, inferred stroke mechanism and risk of recurrence in patients with ischaemic stroke. The question is clinically relevant to optimise secondary stroke prevention investigations and treatment.
Design: We conducted a retrospective analysis of the dabigatran treatment of acute stroke II (DATAS II) trial (ClinicalTrials.
Thromb Haemost
January 2025
Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Background: Fibrinolysis is spatiotemporally well-regulated and greatly influenced by activated platelets and coagulation activity. Our previous real-time imaging analyses revealed that clotting commences on activated platelet surfaces, resulting in uneven-density fibrin structures, and that fibrinolysis initiates in dense fibrin regions and extends to the periphery. Despite the widespread clinical use of direct oral anticoagulants (DOACs), their impact on thrombin-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) and fibrinolysis remains unclear.
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