Synergistic antiplatelet and antithrombotic effects of a prostacyclin analogue (iloprost) combined with a thromboxane antagonist (sulotroban) in guinea pigs and rats.
The stable PGI2-analogue iloprost and the TXA2-receptor antagonist sulotroban were investigated for possible cooperative effects on platelet function and experimental thrombus formation in guinea pigs and rats. Iloprost and sulotroban inhibit intravascular platelet aggregation in guinea pigs and rats induced by the stable endoperoxide U 46.619 and collagen, with iloprost being the more potent and (for collagen) more efficacious drug. Combinations of both compounds show synergistic or additive effects on in vivo platelet function. Thrombus formation in rats induced by vascular damage is strongly reduced by combining doses of iloprost and sulotroban (BM 13.177) which given alone are ineffective. These results suggest a cooperative enhancement of antiplatelet and antithrombotic effects for combinations of iloprost and sulotroban. In view of disadvantages of currently used platelet inhibitors this cooperativity may offer a new approach in antiplatelet therapy.
Witt
W
W
Research Laboratories of Schering AG, Berlin, FRG.
Stürzebecher
S
S
Müller
B
B
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003094:Collagen / Q000633:toxicity; D004357:Drug Synergism; D011464:Epoprostenol / Q000008:administration & dosage / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006168:Guinea Pigs; D016285:Iloprost; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011450:Prostaglandin Endoperoxides, Synthetic / Q000633:toxicity; D051381:Rats; D013449:Sulfonamides / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000517:prevention & control; D013924:Thrombophlebitis / Q000517:prevention & control; D013931:Thromboxanes / Q000037:antagonists & inhibitors
D002317:Cardiovascular Agents; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D013449:Sulfonamides; D013931:Thromboxanes; C040624:sulotroban; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D011464:Epoprostenol; D016285:Iloprost