Merck Research Laboratories, Rahway, NJ 07065, USA.
Platelets. 2010;21(3):191-8. doi: 10.3109/09537100903521611.
Laropiprant (LRPT) has been shown to reduce flushing symptoms induced by niacin and has been combined with niacin for treatment of dyslipidemia. LRPT, a potent PGD(2) receptor (DP1) antagonist that also has modest activity at the thromboxane receptor (TP), may have the potential to alter platelet function either by enhancing platelet reactivity through DP1 antagonism or by inhibiting platelet aggregation through TP antagonism. Studies of platelet aggregation ex vivo and bleeding time have shown that LRPT, at therapeutic doses, does not produce clinically meaningful alterations in platelet function. The present study was conducted to assess platelet reactivity to LRPT using methods that increase the sensitivity to detect changes in platelet responsiveness to collagen and ADP. The responsiveness of platelets was quantified by determining the EC(50) of collagen to induce platelet aggregation ex vivo. At 24 hours post-dose on Day 7, the responsiveness of platelets to collagen-induced aggregation was similar following daily treatment with extended-release niacin (ERN) 2 g/LRPT 40 mg or ERN 2 g. At 2 hours post-dose on Day 7, the EC(50) for collagen-induced platelet aggregation was approximately two-fold higher in the presence of LRPT, consistent with a small, transient inhibition of platelet responsiveness to collagen. There was no clinical difference between treatments for bleeding time, suggesting that this small effect on collagen EC(50) does not result in a clinically meaningful alteration of platelet function in vivo. The results of this highly sensitive method demonstrate that LRPT does not enhance platelet reactivity when given alone or with ERN.
拉罗匹仑（LRPT）已被证明可减轻烟酸引起的潮红症状，并已与烟酸联合用于治疗血脂异常。LRPT 是一种强效 PGD（2）受体（DP1）拮抗剂，对血栓素受体（TP）也具有适度的活性，它可能通过 DP1 拮抗作用增强血小板反应性，或通过 TP 拮抗作用抑制血小板聚集，从而改变血小板功能。体外血小板聚集和出血时间研究表明，LRPT 在治疗剂量下不会对血小板功能产生临床上有意义的改变。本研究旨在使用可提高检测胶原和 ADP 诱导的血小板反应性变化的灵敏度的方法来评估 LRPT 对血小板反应性的影响。通过确定胶原诱导血小板聚集的 EC（50）来定量评估血小板的反应性。在第 7 天的每日治疗后 24 小时，延长释放烟酸（ERN）2 g/LRPT 40 mg 或 ERN 2 g 后，胶原诱导的血小板聚集的反应性相似。在第 7 天的 2 小时后，LRPT 存在时胶原诱导的血小板聚集的 EC（50）约增加两倍，这与胶原诱导的血小板反应性的短暂抑制一致。两种治疗方法的出血时间无临床差异，这表明对胶原 EC（50）的这种小影响不会导致体内血小板功能的临床意义改变。该高度敏感方法的结果表明，LRPT 单独或与 ERN 联合使用时不会增强血小板反应性。
