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QuickView for Dabigatran etexilate (compound)


PubChem
Name: dabigatran etexilate
PubChem Compound ID: 9578572
Molecular formula: C34H41N7O5
Molecular weight: 627.734 g/mol
Synonyms:
BIBR-1048MS; Ethyl 3-(((2-(((4-((((hexyloxy)carbonyl)amino)iminomethyl)phenyl)amino)methyl)-1-methyl-1H-benzimidazol-5-yl)carbonyl)(pyridin-2-yl)amino)propanoate; Rendix; Dabigatran etexilate; 211915-06-9; BIBR-1048; Dabigatran etexilate [INN]
DrugBank
Identification
Name: dabigatran etexilate
Name (isomeric): DB06695
Drug Type: small molecule
Synonyms:
Ethyl 3-[[[4-[[[(hexyloxyl)carbonyl]amino]iminomethyl]phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl](pyridin-2-yl)amino] propanoate (INN); Dabigatran etexilate mesilate (salt form)
Brand: Pradaxa, Rendix, Pradax
Category: Anticoagulants, Antithrombotics, Antithrombotic Agents
CAS number: 211915-06-9
Pharmacology
Indication: Dabigatran is indicated for the prevention of venous thromboembolic events in patients who have undergone elective hip or knee replacement surgery (based on RE-NOVATE, RE-MODEL, and RE-MOBILIZE trials). In 2010, it was approved in the US and Canada for prevention of stroke and systemic embolism in patients with atrial fibrillation (approval based on the RE-LY trial). Contraindications: severe renal impairment (CrCL < 30 ml/min); haemorrhagic manifestations, bleeding diathesis or spontaneous or pharmacologic impairment of haemostasis; lesions at risk of clinically significant bleeding (e.g. extensive cerebral infarction (haemorrhagic or ischemic) in the last 6 months, active peptic ulcer disease); concomitant treatment with P-glycoprotein inhibitors (e.g. oral ketoconazole, verapamil); and those with known hypersensitivity to dabigatran, dabigatran etexilate or any ingredient used in the formulation or component of the container.
Pharmacology:
Dabigatran etexilate is an inactive pro-drug that gets converted to dabigatran, the active form, by esterase-catalyzed hydrolysis in the plasma and liver. Dabigatran, the main active principle in plasma, is a rapid-acting competitive and reversible direct inhibitor of thrombin. Thrombin, a serine protease, is responsible for the conversion of fibri...
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Mechanism of Action: Esterase-catalysed hydrolysis of dabigatran etexilate in the plasma and liver yields the active form, dabigatran. Dabigatran competitively and reversibly binds to thrombin thereby inhibiting its ability to convert fibrinogen to fibrin during the coagulation cascade.
Absorption: Peak plasma concentrations were achieved in 6 hours in post surgical patients. In healthy patients, maximum concentrations were achieved in 0.5 to 2 hours. The absolute bioavailability of dabigatran in the body after administration of dabigatran etexilate was 6.5%. Food does not affect the bioavailability of dabigatran etexilate, but it delays the time to peak plasma concentrations by 2 hours. Oral bioavailability may increase by up to 75% when pellets are taken out of the hydroxypropylmethylcellulose (HPMC) capsule. Therefore, capsules should not be opened and pellets taken alone.
Protein binding: Relatively low binding (34-35%) to plasma proteins.
Biotransformation: Dabigatran is typically metabolised by esterases and microsomal carboxylesterases. CYP450 enzymes do not seem to be involved. Pharmacologically active acylglucoronides are formed via conjugation. Four positional isomers, 1-O, 2-O, 3-O, and 4-O, acylglucuronides exist, each accounting for less than 10% of total plasma dabagatran.
Route of elimination: Mainly excreted in urine (85%). Fecal excretion accounts for 6% of the orally administered dose. Dabigatran is primarily eliminated unchanged via the kidneys at a rate of 100 ml/min corresponding to the glomerular filtration rate.
Half Life: 12-14 hours in healthy volunteers. 14-17 hours in patients treated for prevention of venous thromboembolism following hip- or knee-replacement surgery.
Toxicity: The most common adverse reactions include dyspepsia or gastritis-like symptoms. The approximate lethal dose in rats and mice was observed at single oral doses of > 2000 mg/kg. Oral doses of 600 mg/kg did not induce any toxicologically meaningful changes in dogs and Rhesus monkeys. Dabigatran was well-tolerated in rats and Rhesus monkeys during repeat-dose toxicity studies. No evidence of mutagenic potential.
Affected organisms: Humans and other mammals
Interactions
Food interaction:
St. John's Wort
Drug interaction:
DexamethasoneP-Glycoprotein inducers such as dexamethasone may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.
TrazodoneP-Glycoprotein inducers such as trazodone may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.
VerapamilVerapamil may increase serum concentrations of the active metabolite(s) of dabigatran etexilate, resulting in an increased risk of bleeding. Therapy modification should be considered.
RifampinP-Glycoprotein inducers such as rifampin may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.
QuinidineQuinidine may increase the serum concentration of dabigatran etexilate, resulting in increased bleeding. Consider modification of therapy.
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