Saitoh K, Manabe T, Irino O
Research Laboratory, Grelan Pharmaceutical Co., Ltd., Tokyo, Japan.
Nihon Yakurigaku Zasshi. 1988 Feb;91(2):105-9. doi: 10.1254/fpj.91.105.
The mode for the manifestation of the inhibitory effect of ifenprodil tartrate on platelet aggregation in vivo and ex vivo was studied in mice and men, respectively. The ifenprodil level in plasma reached the maximum in 20 min after oral administration of 30 mg ifenprodil tartrate/kg in mice, and it decreased over a 3 hr period after the administration. On the other hand, the maximal inhibitory effect was observed 60 min after the administration. Thus ifenprodil tartrate manifested its inhibitory effect on platelet aggregation only after the maximum plasma concentration of ifenprodil was reached. The same phenomenon was observed with the inhibitory effects of ifenprodil tartrate on platelet aggregation ex vivo in man. To clarify the reason for the delay in the manifestation of the inhibitory effects of ifenprodil, the ifenprodil contents in mouse platelets after the oral administration of the drug was measured. The pattern of change in the ifenprodil contents in platelets was found to resemble closely the pattern of the change in its inhibitory effects, suggesting that the manifestation of the inhibitory effects on platelet aggregation by oral administration of ifenprodil tartrate was directly related to the ifenprodil contents in platelets rather than the ifenprodil level in plasma.
分别在小鼠和人体中研究了酒石酸艾芬地尔对体内和体外血小板聚集抑制作用的表现方式。给小鼠口服30mg酒石酸艾芬地尔/千克后，血浆中的艾芬地尔水平在20分钟时达到最高，并在给药后3小时内下降。另一方面，给药后60分钟观察到最大抑制作用。因此，酒石酸艾芬地尔仅在达到艾芬地尔血浆浓度最大值后才表现出对血小板聚集的抑制作用。在人体中对酒石酸艾芬地尔体外血小板聚集抑制作用也观察到了相同现象。为了阐明艾芬地尔抑制作用表现延迟的原因，测定了给药后小鼠血小板中的艾芬地尔含量。发现血小板中艾芬地尔含量的变化模式与其抑制作用的变化模式非常相似，这表明口服酒石酸艾芬地尔对血小板聚集抑制作用的表现与血小板中的艾芬地尔含量直接相关，而不是与血浆中的艾芬地尔水平相关。
