Effects of the oral direct thrombin inhibitor ximelagatran on p-selectin expression and thrombin generation in atrial fibrillation.
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.
Wolzt
Michael
M
Department of Clinical Pharmacology, University of Vienna, Vienna, Austria.
Boström
Stig L
SL
Svensson
Mia
M
Wåhlander
Karin
K
Grind
Margaretha
M
Sarich
Troy C
TC
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*
D001384:Azetidines; D001596:Benzylamines; D019007:P-Selectin; C109573:melagatran; C426686:ximelagatran; D013917:Thrombin; D005998:Glycine