Dabigatran: An Oral Novel Potent Reversible Nonpeptide Inhibitor of Thrombin

Eisert, Wolfgang G.; Hauel, Norbert; Stangier, Joachim; Weikel, W.; Clemens, Andreas; Ryn, Joanne van

doi:10.1161/atvbaha.110.203604

Cited by 195 publications

(130 citation statements)

References 27 publications

(30 reference statements)

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“…Mean dabigatran trough levels achieved in patients with any and major bleeding were 111 and 141 ng/mL in the RE-LY trial, respectively [50]. Expected peak and trough concentrations in patients receiving dabigatran 150 mg twice daily are approximately 180 and 90 ng/mL; respectively [51]. The mean dabigatran trough concentration in the RE-LY study was 91 ng/mL (28.2-155 ng/mL, 10th and 90th percentile) [36].…”

Section: Laboratory Assessment To Determine Presence Of Dabigatranmentioning

confidence: 99%

Enhanced Elimination of Dabigatran Through Extracorporeal Methods

2014

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Several pharmacokinetic studies have suggested that dabigatran possesses a number of ideal properties for expedited removal via extracorporeal methods. However, this practice has not been prospectively evaluated in patients with life-threatening bleeding or requiring emergency surgery secondary to dabigatran-associated coagulopathy. The purpose of this literature review is to evaluate the published evidence surrounding extracorporeal removal of dabigatran in the setting of emergency surgery or life-threatening bleeding. A query of MEDLINE, Web of Science, International Pharmaceutical Abstracts, and Google Scholar using the terms dabigatran, dabigatran etexilate, hemodialysis, renal replacement therapy, hemorrhage, and atrial fibrillation was used to retrieve relevant literature. Furthermore, a manual search of the references of the identified literature was performed to capture additional data. Current evidence suggests that extracorporeal removal of dabigatran may play a role in the setting of life-threatening bleeding and emergent surgery. Conflicting evidence exists with regard to the potential for redistribution based on serum dabigatran concentrations. In addition, a number of practicalities must be considered before incorporating this technique in the clinical setting. Extracorporeal removal of dabigatran may be a treatment modality in selected patients who require emergency reversal.

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Section: Laboratory Assessment To Determine Presence Of Dabigatranmentioning

confidence: 99%

Enhanced Elimination of Dabigatran Through Extracorporeal Methods

2014

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“…In a rat model of thrombosis, maximum inhibition of thrombus formation was observed 30 min after oral administration of dabigatran, and when tested in rabbits dabigatran resulted in a dose-dependent inhibition of thrombus weight. In a rat tail bleeding model, bleeding time was not prolonged by dabigatran at an antithrombotic effective dose (Eisert et al, 2010).…”

Section: Pre-clinical Studiesmentioning

confidence: 94%

“…Human thrombin is dose-dependently and competitively inhibited by dabigatran with a Ki of 4.5 nM (Eisert et al, 2010). Dabigatran was well tolerated and showed a dosedependent prolongation of activated partial tissue thromboplastin time in conscious rats and rhesus monkeys.…”

Section: Pre-clinical Studiesmentioning

confidence: 97%

The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism

Mavrakanas

Bounameaux

2011

Pharmacology & Therapeutics

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Thromboembolic disorders are among the major causes of morbidity and mortality, and anticoagulation remains the cornerstone of prevention and treatment of these disorders. Although effective, the well-established agents have significant drawbacks. Heparin, low molecular weight heparin, and fondaparinux must be given parenterally, which is inconvenient for long-term or home use. The orally administered vitamin K antagonists (such as warfarin) have a slow onset of action, thus requiring bridging therapy with a parenteral agent when immediate anticoagulation is needed (e.g. inpatients with acute deep vein thrombosis). Because vitamin K antagonists produce a variable anticoagulant response as a result of multiple drug-drug and food-drug interactions and genetic polymorphisms, frequent coagulation monitoring and dose adjustment are required to ensure a therapeutic level of anticoagulation, which is inconvenient for both patients and physicians. In the search for new agents to overcome the drawbacks associated with traditional agents, direct Factor Xa inhibitors (e.g. rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitors (e.g. dabigatran etexilate) have been developed and are undergoing late-stage clinical evaluation for the prevention and treatment of thromboembolic disorders. These new oral agents have already shown promise in large-scale clinical studies and data suggest that we have entered a new era with novel drugs that are closer than ever to the 'ideal anticoagulant'. Because these new oral agents have a rapid onset of action and can be given at fixed doses without the need for routine coagulation monitoring, they may simplify treatment paradigms and are expected to improve overall clinical outcome

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“…Su excreción es mayoritariamente renal (80%), y por ello, está contraindicado en pacientes con clearance de creatinina <30ml/min. 18,19 Inhibidores de FXa Actúan en una etapa previa en la cascada de la coagulación. Inhiben al FXa, parte del complejo protrombinasa (FXa-FV) y al FXa asociado a trombina.…”

Section: Nuevos Anticoagulantes Orales (Tabla 1)unclassified

Nuevos anticoagulantes orales: actualización

Berkovits

Mezzano

2017

Rev Chil Cardiol

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Recibido el 19 de junio 2017 / Aceptado el 11 de agosto 2017Rev Chil Cardiol 2017; 36: 254 -263 Resumen:Los anticoagulantes orales clásicos del tipo cumarinas han estado disponibles para uso clínico por más de medio siglo. Tienen gran eficacia para tratar o prevenir trombosis y tromboembolias, y son drogas cuyo uso ha aumentado con el mejor conocimiento clínico, el aumento de los factores de riesgo y el envejecimiento de la población. Entre sus desventajas se incluyen la alta variabilidad de su efecto en cada sujeto y entre individuos, la influencia del nivel de ingesta de vitamina K, la necesidad de control periódico del nivel de anticoagulación, su interacción con múltiples drogas. Si bien, el rango terapéutico está estandarizado, es estrecho, haciendo que el tiempo en rango terapéutico sea de ≈ 60%.Por estas limitaciones, se han creado nuevos anticoagulantes orales (NACOs), siendo progresivamente aprobados para uso clínico por agencias internacionales. Genéricamente, son de 2 tipos: inhibidores selectivos de trombina (dabigatrán) o de FXa (rivaroxabán, apixabán, edoxabán y betrixabán). Los NACOs se caracterizan por su dosificación una o dos veces al día, rapidez de acción, corta vida media en la circulación, predictibilidad de su efecto, dosis preestablecidas, sin necesidad de control periódico y con escasa o nula interacción con otras drogas. Estas ventajas no se han traducido en la mayoría de los ensayos en un superior efecto antitrombótico o menor riesgo de sangrado, y en su mayoría (salvo dabigatrán) carecen de antídoto específico demostrado.

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Dabigatran: An Oral Novel Potent Reversible Nonpeptide Inhibitor of Thrombin

Cited by 195 publications

References 27 publications

Enhanced Elimination of Dabigatran Through Extracorporeal Methods

Enhanced Elimination of Dabigatran Through Extracorporeal Methods

The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism

Nuevos anticoagulantes orales: actualización

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