Dabigatran
Dabigatran. Dabigatran etexilate is an oral prodrug; esterase hydrolysis in gut/liver/plasma yields active dabigatran, a reversible, competitive… Oral half-life 14 h.
Dabigatran etexilate is an oral prodrug; esterase hydrolysis in gut/liver/plasma yields active dabigatran, a reversible, competitive direct thrombin inhibitor that binds both free and fibrin-bound thrombin. Absorption from the gut requires an acidic microenvironment — hence the tartaric-acid pellet formulation and the tendency for dyspepsia. ~80% renal elimination makes creatinine clearance the dominant determinant of exposure. Specific reversal agent: idarucizumab.
PK: A NOTE THAT DESCRIBED THE WRONG STUDY ENTIRELY. Its effect-compartment note read "IV dabigatran CARDIAC SURGERY, ROTEM CT endpoint"; the paper is FIVE SHEEP and the endpoint is thromboelastometric R-time. The quoted number and arithmetic were both right, but the note invented a human clinical population — a step beyond the batch-3 case where a note merely quoted an absent string. It is also contradicted by this record own pharmacokinetic citation, which reports "a rapid onset of action WITHOUT A TIME DELAY", and the entire dabigatran effect-compartment literature is animal-intravenous. Removed. A DOSE-BASIS ERROR IS LOGGED RATHER THAN SILENTLY FIXED: mw 471.51 is the ACTIVE species, correct for its half-life and volume, but the administered molecule is dabigatran ETEXILATE at 627.73, so a 150 mg dose is converted to moles 1.331x too high. This is the mirror image of the batch-4 prodrug failure. V 1860 L is the published apparent value with F pinned to 1, replacing an unsourced 60 L and a 0.07 that appears in no abstract. The half-life is the upper endpoint of a stated 12-14 h; no point value is published.
Pharmacokinetics
- Oral — t½ 14 h · F 100% · Vd 1860 L
Related compounds
Sources: PMID:18399711, PMID:15911722, PMID:17506785, PMID:18076218