Payne Christopher D, Li Ying G, Brandt John T, Jakubowski Joseph A, Small David S, Farid Nagy A, Salazar Daniel E, Winters Kenneth J
Lilly Research Laboratories, Eli Lilly and Company, Windlesham, Surrey, UK.
Platelets. 2008 Jun;19(4):275-81. doi: 10.1080/09537100801891640.
Prasugrel, a novel P2Y(12) antagonist, achieves faster onset and greater inhibition of platelet aggregation than clopidogrel 300 and 600 mg loading doses (LD). We studied the safety, time course, and level of platelet inhibition when switching directly from clopidogrel 75 mg maintenance dose (MD) to a prasugrel 60 mg LD/10 mg MD or 10 mg MD regimen. Healthy subjects (n = 39) on aspirin (81 mg/d) received a clopidogrel 600 mg LD followed by 10 days of clopidogrel MD (75 mg/d). Subjects were then randomized without a washout period to prasugrel 60 mg LD (n = 16) followed by 10 days of prasugrel MD (10 mg/d) or to prasugrel MD (10 mg/d, n = 19) for 11 days. Maximal platelet aggregation (MPA) to 20 microM ADP was measured by turbidimetric aggregometry. In subjects on clopidogrel 75 mg MD, mean MPA decreased from 39 to 12% by 30 minutes, and to 5% by 1 hour after a prasugrel 60 mg LD (p < 0.001 for both) and from 37 to 28% (p < 0.001) by 1 hour after a prasugrel 10 mg MD. During prasugrel MD, a new pharmacodynamic steady state MPA of approximately 24% (p < 0.01 vs. clopidogrel MD) occurred within four to five days of switching from clopidogrel. Changing from clopidogrel to prasugrel did not increase bleeding episodes or other adverse events. Switching directly from clopidogrel MD to either prasugrel LD or MD was well tolerated and resulted in significantly greater levels of platelet inhibition than a clopidogrel 75 mg MD.
普拉格雷是一种新型P2Y(12)拮抗剂，与氯吡格雷300毫克和600毫克负荷剂量（LD）相比，其起效更快，对血小板聚集的抑制作用更强。我们研究了从氯吡格雷75毫克维持剂量（MD）直接转换为普拉格雷60毫克LD/10毫克MD或10毫克MD方案时血小板抑制的安全性、时间进程和水平。服用阿司匹林（81毫克/天）的健康受试者（n = 39）接受氯吡格雷600毫克LD，随后服用10天氯吡格雷MD（75毫克/天）。然后，受试者在无洗脱期的情况下被随机分为接受普拉格雷60毫克LD（n = 16），随后服用10天普拉格雷MD（10毫克/天）或接受普拉格雷MD（10毫克/天，n = 19），持续11天。通过比浊法聚集测定法测量对20微摩尔ADP的最大血小板聚集（MPA）。在服用氯吡格雷75毫克MD的受试者中，在给予普拉格雷60毫克LD后30分钟，平均MPA从39%降至12%，1小时后降至5%（两者p < 0.001）；在给予普拉格雷10毫克MD后1小时，平均MPA从37%降至28%（p < 0.001）。在普拉格雷MD期间，从氯吡格雷转换后的四到五天内出现了新的药效学稳态MPA，约为24%（与氯吡格雷MD相比，p < 0.01）。从氯吡格雷转换为普拉格雷并未增加出血事件或其他不良事件。直接从氯吡格雷MD转换为普拉格雷LD或MD耐受性良好，且导致的血小板抑制水平明显高于氯吡格雷75毫克MD。
