Ardlie N G
Thromb Haemost. 1977 Oct 31;38(3):612-9.
Halofenate--free acid (HFA), the major metabolite of the hypolipidemic drug, halofenate, inhibited platelet aggregation induced by collagen and sodium arachidonate and blocked the second phase of aggregation caused by ADP, thrombin and epinephrine in human platelet-rich plasma. The aggregation of washed platelets by thrombin and collagen was also blocked. HFA also inhibited the release by thrombin and collagen of 5-hydroxytryptamine from dense granules of platelets and the release by thrombin of beta-glucuronidase from platelet alpha-granules. These inhibitory effects were concentration and time-dependent. HFA decreased platelet factor 3 activity by 31% and also inhibited the incorporation of 14C-acetate and U-14C-glucose into platelet lipids by 89% and 56% respectively. Thrombin-induced lipid peroxidation and prostaglandin formation was investigated by measuring the by-product malonyldialdehyde, and this was found to be inhibited by HFA. It is suggested that the effect of HFA on aggregation is attributable to inhibition of the release reaction which may in turn be a consequence of the effects of the drug on platelet lipid synthesis.
降脂药物卤芬酯的主要代谢产物卤芬酯游离酸（HFA），可抑制富含人血小板血浆中由胶原和花生四烯酸钠诱导的血小板聚集，并阻断由ADP、凝血酶和肾上腺素引起的第二阶段聚集。凝血酶和胶原对洗涤后血小板的聚集也受到阻断。HFA还抑制凝血酶和胶原从血小板致密颗粒中释放5-羟色胺，以及凝血酶从血小板α颗粒中释放β-葡萄糖醛酸酶。这些抑制作用具有浓度和时间依赖性。HFA使血小板因子3活性降低31%，还分别抑制14C-乙酸盐和U-14C-葡萄糖掺入血小板脂质89%和56%。通过测量副产物丙二醛研究了凝血酶诱导的脂质过氧化和前列腺素形成，发现其受到HFA抑制。提示HFA对聚集的作用归因于对释放反应的抑制，而这反过来可能是该药物对血小板脂质合成作用的结果。
