Stroke, Vol 17, 450-454, Copyright © 1986 by American Heart Association
S Kaplan, LR Sauvage, KF Marcoe, M Zammit, HD Wu, SR Mathisen and M Walker
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.
ARTICLES
A new combination therapy for selective and prolonged antiplatelet effect: results in the dog