Ex vivo anti-platelet effects of isocarbacyclin methyl ester incorporated in lipid microspheres in rabbits.
Effect of TTC-909, a chemically stable isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090) incorporated in lipid microspheres, on platelet aggregation was tested in conscious rabbits. TTC-909 significantly inhibited platelet aggregation induced by ADP at early times after bolus i.v. injection from the dose of 0.3 micrograms/kg in a dose-dependent manner. Similarly, TTC-909 significantly inhibited platelet aggregation induced by ADP during the venous infusion from the dose of 100 ng/kg/min, also in a dose-dependent manner. The anti-platelet effect of TTC-909 was observed at a dose lower than that inducing hypotensive effect when given as both bolus i.v. and venous infusion. On the other hand, prostaglandin (PG) E1 (LM)--PGE1 incorporated in lipid microspheres--reduced blood pressure without having an anti-platelet effect. These results indicate that TTC-909 may be a potent anti-thrombotic drug.
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001772:Blood Cell Count; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits
D004337:Drug Carriers; D008081:Liposomes; D010975:Platelet Aggregation Inhibitors; C068518:TTC 909; D011464:Epoprostenol; D000527:Alprostadil