Dabigatran etexilate

Dabigatran etexilate Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  Dabigatran etexilate is an orally administered pro-drug of dabigatran, which is a direct inhibitor of thrombin and a potent anticoagulant. The serine protease thrombin is the final mediator in the coagulation cascade that leads to the production of fibrin, the main protein component of blood clots. Thrombin is also a potent activator of platelets. Consequently, thrombin inhibitors have found utility as anticoagulants in treating arterial and venous thrombosis. Warfarin, although orally available, has a narrow therapeutic index and requires frequent monitoring and dosage adjustment. Low-molecular-weight heparins provide better safety profile and less inter-patient variability; however, these agents are only available for parenteral administration. Direct thrombin inhibitors (DTIs) are a new class of anticoagulants that act by directly binding to thrombin at its catalytic or fibrinogen-binding sites, or both. Unlike the heparins, DTIs do not require the activation of secondary factors such as antithrombin to derive their activity, which makes their action more predictable. In addition, their ability to inhibit both free and clot-bound thrombin predisposes them for enhanced anticoagulation effect.

• Originator

  Boehringer Ingelheim (Germany)

• Verwenden

  BIBR-1048 (Dabigatran) is an anticoagulant from the class of the direct thrombin inhibitors. It is being studied for various clinical indications and in many cases it offers an alternative to warfarin as the preferred orally administered blood thinner sin

• Verwenden

  Dabigatran Etexilate is an oral anticoagulant and direct thrombin inhibitor.

• Definition

  ChEBI: An aromatic amide obtained by formal condensation of the carboxy group of 2-{[(4-{N'-[(hexyloxy)carbonyl]carbamimidoyl}phenyl)amino]methyl}-1-methyl-1H-benzimidazole-5-carboxylic acid with the secondary amino group of thyl N-pyridin-2-yl-beta-alaninate. A prodrug for dabigatran, a thrombin inhibitor and anticoagulant which is used for the prevention of stroke and systemic embolism.

• Trademarks

  Pradaxa

• Synthese

  The chemical synthesis of dabigatran etexilate starts with the acylation of ethyl 3-(2-pyridylamino)propionate with 4-(methylamino)-3-nitrobenzoyl chloride to produce the corresponding amide. Subsequent reduction of the nitro group by catalytic hydrogenation, and cyclization of the resultant phenylenediamine with N-(4-cyanophenyl)glycine leads to a benzimidazole intermediate. The cyano group is then transformed into an amidine by employing the Pinner reaction. Finally, acylation of the amidino group with hexyl chloroformate gives rise to dabigatran etexilate.

• in vitro

  dabigatran showed anticoagulant effects in a concentration-dependent manner. it doubled the activated partrial thromboplastin time, prothrombin time and ecarin clotting in human ppp. [1]

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Analgesics: possible increased risk of bleeding with NSAID’s; increased risk of haemorrhage with ketorolac or IV diclofenac - avoid.
  Anti-arrhythmics: concentration increased by amiodarone, reduce dose of dabigatran; concentration increased by dronedarone - avoid.
  Antibacterials: concentration reduced by rifampicin - avoid; possibly increased risk of bleeding with clarithromycin.
  Anticoagulants: increased risk of haemorrhage with other anticoagulants - avoid.
  Antidepressants: possible increased risk of bleeding with SSRIs; concentration possibly reduced by St John’s wort - avoid.
  Antifungals: concentration increased by ketoconazole and possibly itraconazole - avoid
  Ciclosporin: concentration possibly increased by ciclosporin - avoid.
  Sulfinpyrazone: possible increased risk of bleeding.
  Tacolimus: concentration possibly increased by tacrolimus - avoid.
  Ticagrelor: concentration of dabigatran increased.
  Verapamil: reduce dose of dabigatran to 150 mg daily, 75 mg in GFR=30-50mL/min.

• Stoffwechsel

  Dabigatran etexilate is a prodrug which does not exhibit any pharmacological activity. After oral administration, dabigatran etexilate is rapidly absorbed and converted to dabigatran by esterase-catalysed hydrolysis in plasma and in the liver. Dabigatran is a potent, competitive, reversible direct thrombin inhibitor and is the main active principle in plasma.
  Mainly excreted in the urine (85%) and 6% via the faeces.

• Einzelnachweise

  1. wienen w, stassen jm, priepke h et al. in-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. thromb haemost. 2007 jul;98(1):155-62.2. connolly sj, ezekowitz md, yusuf s et al. dabigatran versus warfarin in patients with atrialfibrillation. n engl j med. 2009 sep 17;361(12):1139-51.

Dabigatran etexilate Upstream-Materialien And Downstream Produkte

Dabigatran etexilate Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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