塩酸ジラゼプとアスピリン併用投与時の血小板凝集能ならびに血管壁ＰＧＩ２産生能

Abstract

Aspirin (ASA) has been used as an antiplatelet drug in clinical trials to treat and prevent thrombosis. However, high doses of ASA have disadvantage not only inducing gastric lesion but also inhibiting prostacyclin (PGI2) generation in vessel wall. The possibility of useful combined therapy of dilazep (DZP), a coronary vasodilator, and low doses of ASA was described.Platelet aggregation in platelet-rich plasma (PRP) was measured according to the method of Born et al. using the platelet aggregometer (NKK, Hematracer-1). 6-keto-PGF1α in reaction medium where isolated aortic rings had been incubated at 37°C for 10min. was assayed for estimation of aortic PGI2 production using the 6-keto-PGF1α RIA kit (New England Nuclear).A synergetic inhibitory action of the two drugs was demonstrated on platelet aggregation using rabbit PRP in vitro. In ex vivo experiments using rats 3hr after the oral administration, ASA alone inhibited platelet aggregation at doses more than 6.25mg/kg. However, it prevented aortic PGI2 generation at 25mg/kg or above. On the other hand, the combined doses of 6.25mg/kg ASA+100mg/kg DZP and 6.25mg/kg ASA+300mg/kg DZP exhibited markedly inhibitory effects on platelet aggregation corresponding to 25mg/kg ASA alone, but had no significant effect on aortic PGI2 generation.In time-course experiments using rabbits, the combination of 300mg/kg DZP and 6.25mg/kg ASA showed an enhancement of antiplatelet effect from 3 to 6hr after the oral administration. The combination effect of ASA (30mg) and DZP (100mg) on platelet aggregation was also observed in healthy volunteers from 3 to 6hr after the dose.Therefore, a desirable antiplatelet therapy may be performed with a combined dose of 100mg DZP and a very low dose of ASA.