Direct thrombin inhibitors pharmacokinetics

Mechanism of Action A direct thrombin inhibitor that reversibly binds to thrombin-active sites. Inhibits thrombin-catalyzed or thrombin-induced reactions, including fibrin formation, activation of coagulant factors V, VIII, and XIII also inhibits protein C formation, and platelet aggregation. Therapeutic Effect Produces anticoagulation. Pharmacokinetics Following IV administration, distributed primarily in extracellular fluid. Protein binding 54%. Metabolized in the liver. Primarily excreted in the feces, presumably through biliary secretion. Half-life 39-51 min. 

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Sarich TC, Schutzer KM, Dorani H, et al. No pharmacokinetic or pharmacodynamic interaction between atorvastatin and the oral direct thrombin inhibitor ximelagatran. J Clin Pharmacol 2004 44 928-934. 

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Sarich TC, Teng R, Peters GR, et al. No influence of obesity on the pharmacokinetics and pharmacodynamics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran. Clin Pharmacokinet 2003 42 485 -92,... 

StangierJ, Eriksson Bl, Dahl OE, etal. Pharmacokinetic profile of the oral direct thrombin inhibitor dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement. J Clin Pharmacol 2005 45 555-563. 

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Slangier J, Stable H, Rathgen K, Roth W, Shakeri-Nejad K. Pharmacokinetics and pharmacodynamics of dabigatran etexi-late, an oral direct thrombin inhibitor, are not affected by moderate hepatic impairment. J Clin Pharmacol 2008 48(12) 1411-9. 

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