[Clinical and preclinical pharmacology of KC-764, a novel antiplatelet agent].
Preclinical pharmacological studies showed that KC-764 was more potent and more selective in inhibiting platelet aggregation than aspirin. The concentration of KC-764 for inhibiting PGI2 production in the aorta was 70 times higher than that for inhibiting TXA2 in platelets. Antiplatelet action of KC-764 was augmented by plasma components. This augmentation by plasma may lead to selective antiplatelet activity. KC-764 has been investigated for platelet function in patients with chronic cerebral infarction. KC-764 at 10, 20 and 40 mg b i d, inhibited platelet aggregation induced by arachidonic acid, collagen, and ADP, and its potency was almost equal to aspirin at 100-330 mg daily. Plasma TXB2 levels were markedly depressed by KC-764 but plasma 6-keto-PGF1 alpha levels were not influenced. On the contrary, aspirin depressed both plasma prostanoids. These findings suggest that KC-764 can overcome the 'aspirin dilemma'.
Yoshioka
M
M
First Department of Internal Medicine, Kansai Medical University.
Soga
T
T
Mase
K
K
Yasunaga
K
K
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000368:Aged; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D003094:Collagen / Q000037:antagonists & inhibitors; D016861:Cyclooxygenase Inhibitors; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009539:Nicotinic Acids / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011453:Prostaglandins / Q000378:metabolism
D001643:Bridged Bicyclo Compounds; D016861:Cyclooxygenase Inhibitors; D009539:Nicotinic Acids; D010975:Platelet Aggregation Inhibitors; D011453:Prostaglandins; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; C074536:KC 764