Effect of a synthetic thrombin inhibitor MCI-9038 on experimental models of disseminated intravascular coagulation in rabbits.
We examined the effect of a synthetic thrombin inhibitor, MCI-9038, on two experimental animal models of disseminated intravascular coagulation (DIC). In a model that DIC induced by the intravenous infusion of thrombin, MCI-9038 suppressed the decrease of platelet count by about 50% at a dose of 0.2 micrograms/kg/min and almost completely at 2 micrograms/kg/min. When MCI-9038 was administered orally, the suppressive effect was also observed. Heparin suppressed the platelet count decrease by about 50% at 1 unit/kg/min. In another model of DIC induced by lactic acid and tissue thromboplastin infusion, MCI-9038 prevented the decrease of platelet count and the consumption of coagulation factors. The suppression effect by about 50% on these changes was observed at a dose of 3.16 micrograms/kg/min. Thromboelastogram pattern indicating the consumption coagulopathy in control experiments was normalized by the MCI-9038 administration. Heparin suppressed the decrease of fibrinogen content as effectively as MCI-9038, but it was less effective on the platelet count decrease. From these results, it was concluded that MCI-9038 might be useful for the treatment of DIC.
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D000991:Antithrombins / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D008297:Male; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000627:therapeutic use*; D010976:Platelet Count / Q000187:drug effects; D011817:Rabbits; D013449:Sulfonamides; D013925:Thromboplastin / Q000494:pharmacology
D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D000990:Antithrombin III; D005340:Fibrinogen; D006493:Heparin; D013925:Thromboplastin; D001120:Arginine; C031942:argatroban