Graff Jochen, Arabmotlagh Mohammed, Cheung Raymond, Geisslinger Gerd, Harder Sebastian
Pharmazentrum Frankfurt/ZAFES(Center of Drug Research, Development, and Safety), Institute of Clinical Pharmacology, University Hospital Frankfurt am Main, Frankfurt, Germany.
Clin Ther. 2007 Mar;29(3):438-47. doi: 10.1016/s0149-2918(07)80082-8.
Based on a PubMed search of the literature using the terms parecoxib, platelets, thromboxane, bleeding, and platelet aggregation, the effects of parecoxib on platelet function have not fully been established under clinical conditions.
The aim of this study was to determine platelet aggregation, thromboxane B(2) (TxB(2)) formation, and plasma concentrations with the use of parecoxib in postoperative pain management.
This double-blind, randomized, parallel-group trial was conducted at the University Hospital for Orthopedic Surgery, Friedrichsheim, Frankfurt, Germany. Male and female patients aged 18 to 55 years and scheduled to undergo routine partial meniscectomy (or a similar arthroscopic procedure) were eligible. All patients received dose-adjusted enoxaparin before surgery and parecoxib 40 mg BID or dipyrone 1000 mg QID. Blood samples were drawn before first injection (predose) and at 0.5, 2, and 6 hours after injection. Platelet aggregation (expressed as percentage of the maximal light transmittance [A(max)]) was induced with arachidonic acid (A(max)AA) and collagen (A(max)CO). TxB(2) formation was determined using enzyme-linked immunosorbent assay.
This study included 26 patients. In both treatment groups, 8 males and 5 females, all white, were enrolled. In the dipyrone group, the mean age was 48 years (range, 32-61 years) and the mean weight was 85 kg (range, 63-122 kg); in the parecoxib group, the mean age was 47 years (range, 31-61 years) and the mean weight was 81 kg (range, 57-100 kg). Median (interquartile range [IQR]) predose values for A(max)AA were 76% (65%-83%) in the parecoxib group and 87% (80%-89%) in the dipyrone group. At 0.5 hour after injection, A(max)AA was 52% (5%-77%) with parecoxib and 8% (0%-11%) with dipyrone (P=0.004). At 2 hours after injection, A(max)AA was 78% (72%-80%) in the parecoxib group versus 7% (5%-11%) in the dipyrone group (P<0.001). At 6 hours after study drug administration, no treatment differences were found. For A(max)CO, no statistically significant differences were found. Consistent with the stronger inhibition of aggregation, patients who received dipyrone had lower TxB(2) formation values. Six hours after parecoxib administration, mean TxB(2) formation was significantly enhanced compared with predose values (132 ng/mL [IQR, 62-228 ng/mL] vs 185 ng/mL [IQR, 135-239 ng/mL]; P=0.05).
Platelet aggregation and TxB(2) formation were significantly lower for 6 hours in dipyronetreated patients compared with parecoxib-treated patients. In contrast, TxB(2) formation was increased with parecoxib 6 hours after administration compared with pretreatment values. In this small study, parecoxib did not affect platelet aggregation in a population of patients undergoing routine partial meniscectomy (or a similar arthroscopic procedure) under clinical conditions.
基于使用帕瑞昔布、血小板、血栓素、出血和血小板聚集等术语在PubMed上对文献进行的检索，帕瑞昔布在临床条件下对血小板功能的影响尚未完全明确。
本研究旨在确定在术后疼痛管理中使用帕瑞昔布时的血小板聚集、血栓素B₂（TxB₂）形成及血浆浓度。
这项双盲、随机、平行组试验在德国法兰克福弗里德里希斯海姆大学骨科医院进行。年龄在18至55岁且计划接受常规部分半月板切除术（或类似关节镜手术）的男性和女性患者符合条件。所有患者在手术前接受剂量调整的依诺肝素，以及帕瑞昔布40mg每日两次或安乃近1000mg每日四次。在首次注射前（给药前）以及注射后0.5、2和6小时采集血样。用花生四烯酸（A(max)AA）和胶原（A(max)CO）诱导血小板聚集（以最大透光率[A(max)]的百分比表示）。使用酶联免疫吸附测定法测定TxB₂的形成。
本研究纳入26例患者。两个治疗组均纳入8例男性和5例女性，均为白人。在安乃近组中，平均年龄为48岁（范围32 - 61岁），平均体重为85kg（范围63 - 122kg）；在帕瑞昔布组中，平均年龄为47岁（范围31 - 61岁），平均体重为81kg（范围57 - 100kg）。帕瑞昔布组给药前A(max)AA的中位数（四分位间距[IQR]）为76%（65% - 83%），安乃近组为87%（80% - 89%）。注射后0.5小时，帕瑞昔布组的A(max)AA为52%（5% - 77%），安乃近组为8%（0% - 11%）（P = 0.004）。注射后2小时，帕瑞昔布组的A(max)AA为78%（72% - 80%），安乃近组为7%（5% - 11%）（P < 0.001）。在给予研究药物6小时后，未发现治疗差异。对于A(max)CO，未发现统计学上的显著差异。与更强的聚集抑制作用一致，接受安乃近的患者TxB₂形成值较低。帕瑞昔布给药6小时后，平均TxB₂形成与给药前值相比显著升高（132ng/mL[IQR，62 - 228ng/mL]对185ng/mL[IQR，135 - 239ng/mL]；P = 0.05）。
与帕瑞昔布治疗的患者相比，接受安乃近治疗的患者血小板聚集和TxB₂形成在6小时内显著降低。相反，帕瑞昔布给药6小时后TxB₂形成与治疗前值相比增加。在这项小型研究中，在临床条件下，帕瑞昔布对接受常规部分半月板切除术（或类似关节镜手术）的患者群体的血小板聚集没有影响。
