Ridogrel, a combined thromboxane synthase inhibitor and receptor blocker, decreases elevated plasma beta-thromboglobulin levels in patients with documented peripheral arterial disease.
The combination of thromboxane synthase inhibition with thromboxane receptor antagonism has been shown to result in a strong inhibition of platelet aggregation and a prolongation of the bleeding time (Gresele et al., J. Clin Invest 1987; 80: 1435-45). Ridogrel is a single molecule that efficiently achieves both inhibitions in human volunteers. The present study was performed in patients with obstructive peripheral arterial disease and elevated plasma beta-thromboglobulin levels. Patients were treated with either 2 x 300 mg ridogrel or 2 x 300 mg placebo per day for 2 1/2 days, according to a double blind randomised parallel design. Plasma beta-thromboglobulin decreased significantly throughout active treatment starting within 2 h after administration; serum and urinary immunoreactive TxB2 levels and urinary 11-dehydro-TxB2 excretion were significantly lower and serum PGE2 and 6-keto-PGF1 alpha levels significantly higher with ridogrel; no changes were observed in the placebo-treated group. In conclusion this study demonstrates a reduction of platelet activation in vivo by ridogrel.
Hoet
B
B
Center for Thrombosis and Vascular Research, K.U. Leuven, Belgium.
Arnout
J
J
Van Geet
C
C
Deckmyn
H
H
Verhaeghe
R
R
Vermylen
J
J
D000368:Aged; D000369:Aged, 80 and over; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D006801:Humans; D010421:Pentanoic Acids / Q000627:therapeutic use*; D015539:Platelet Activation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000378:metabolism; D011453:Prostaglandins / Q000097:blood; D011725:Pyridines / Q000627:therapeutic use*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D001620:beta-Thromboglobulin / Q000187:drug effects*
D010421:Pentanoic Acids; D011453:Prostaglandins; D011725:Pyridines; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D001620:beta-Thromboglobulin; D010978:Platelet Factor 4; D013929:Thromboxane B2; D013930:Thromboxane-A Synthase; C060219:ridogrel