title: Effects of the oral direct thrombin inhibitor ximelagatran on p-selectin expression and thrombin generation in atrial fibrillation.
abstract: This study investigated the pharmacodynamic effects of the oral direct thrombin inhibitor ximelagatran on platelet activation and thrombin generation in patients with nonvalvular atrial fibrillation. Using an open, group-matched study design, the effects of ximelagatran (36 mg twice daily for 5 days) were studied in 12 patients with permanent nonvalvular atrial fibrillation and in 12 healthy controls. After ximelagatran for 5 days, elevated platelet P-selectin expression in atrial fibrillation patients was lowered to that during coumarin treatment or in controls but had no effect in control subjects. Using the endogenous thrombin potential as a marker, ximelagatran decreased and delayed thrombin generation in both groups. In conclusion, direct thrombin inhibition with ximelagatran reduced elevated platelet P-selectin expression and inhibited thrombin generation.
authors: Department of Clinical Pharmacology, University of Vienna, Vienna, Austria.
authors: Michael
authors: M
authors: Wolzt
authors: Stig L
authors: SL
authors: Boström
authors: Mia
authors: M
authors: Svensson
authors: Karin
authors: K
authors: Wåhlander
authors: Margaretha
authors: M
authors: Grind
authors: Troy C
authors: TC
authors: Sarich
mesh_terms: D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy*; D001384:Azetidines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D001596:Benzylamines; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000097:blood; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000096:biosynthesis / Q000187:drug effects*; D015539:Platelet Activation / Q000187:drug effects; D013917:Thrombin / Q000037:antagonists & inhibitors; D013927:Thrombosis / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*
chemical_list: D001384:Azetidines; D001596:Benzylamines; D019007:P-Selectin; C109573:melagatran; C426686:ximelagatran; D013917:Thrombin; D005998:Glycine