A new combination therapy for selective and prolonged antiplatelet effect: results in the dog.
This study characterizes the effect of dazmegrel, a thromboxane synthetase inhibitor, on platelet function in the dog and introduces its potential use in combination with aspirin therapy. Ex vivo testing of dazmegrel alone was performed with three dosages and three administration regimens. Platelet aggregation response, malondialdehyde formation and prostaglandin metabolites generation were evaluated. To maintain complete thromboxane A2 inhibition, dazmegrel had to be given 3 times per day at dosages of not less than 6 mg/kg. The same result was achieved with a single daily administration of combined dazmegrel and aspirin in equal dosages of 3 mg/kg. Dazmegrel, both alone and with aspirin, increased and sustained heightened levels of prostacyclin, unlike the simultaneous inhibition of both prostaglandin metabolites seen with aspirin therapy alone. Because the combination of dazmegrel and aspirin effectively blocks thromboxane A2 formation and also enhances prostacyclin formation, the synergistic action of these agents increases their combined antiplatelet effect to a level not attainable by either agent alone. The significance of this combined therapy warrants further experimental study and may soon merit clinical trial for the prevention of stroke and other major thrombotic complications.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000096:biosynthesis; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis; D013997:Time Factors
D005343:Fibrinolytic Agents; D007093:Imidazoles; C039242:dazmegrel; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D001241:Aspirin