Van Ryn Joanne, Kink-Eiband Monika, Kuritsch Ingrid, Feifel Ulrich, Hanft Gertraud, Wallenstein Gudrun, Trummlitz Guenter, Pairet Michel
Boehringer Ingelheim Pharma GmbH and Co. KG, Birkendorfer Str. 65, 88397 Biberach, Germany.
J Clin Pharmacol. 2004 Jul;44(7):777-84. doi: 10.1177/0091270004266623.
This study determined if meloxicam, a selective cyclooxygenase (COX)-2 inhibitor, interferes with the antiplatelet effect of aspirin using platelet aggregation and thromboxane (Tx) B(2) endpoints in healthy volunteers. Eight male and 8 female volunteers participated in this open-label, randomized, two-treatment, two-way crossover trial. Treatment 1 was meloxicam (15 mg qd) over 4 days, and then aspirin (100 mg qd) was ingested 2 hours after meloxicam for an additional 7 days. Blood samples were taken 2, 6, and 24 hours after the last dose. Treatment 2 consisted of only aspirin (100 mg) over 2 days. Samples were taken at the same time points. Each subject received both treatments with a 2-week washout between the treatment periods. Treatments were safe and well tolerated. The initial 4-day treatment with meloxicam had no effect on platelet aggregation but reduced serum TxB(2) by 64% +/- 19%. Addition of aspirin (100 mg qd) for 7 days resulted in complete inhibition of aggregation and TxB(2) for 24 hours. Two-day treatment with only 100 mg aspirin also resulted in complete inhibition of platelet aggregation and TxB(2). These results indicate that meloxicam does not affect the ability of aspirin to inhibit COX-1 in platelets, thereby allowing aspirin to effectively prevent platelet aggregation and reduce TxB(2) levels, and that meloxicam is selective for COX-2.
本研究通过在健康志愿者中检测血小板聚集和血栓素(Tx)B2指标,来确定选择性环氧化酶(COX)-2抑制剂美洛昔康是否会干扰阿司匹林的抗血小板作用。16名志愿者(8男8女)参与了这项开放标签、随机、双治疗、双向交叉试验。治疗1为美洛昔康(15毫克,每日一次)服用4天,然后在服用美洛昔康2小时后摄入阿司匹林(100毫克,每日一次),再持续7天。在最后一剂药物服用后2小时、6小时和24小时采集血样。治疗2为仅服用阿司匹林(100毫克),持续2天。在相同时间点采集样本。每个受试者接受两种治疗,治疗期间间隔2周的洗脱期。治疗安全且耐受性良好。最初4天的美洛昔康治疗对血小板聚集无影响,但可使血清TxB2降低64%±19%。加用阿司匹林(100毫克,每日一次)7天可导致聚集和TxB2在24小时内完全被抑制。仅服用100毫克阿司匹林进行2天治疗也可导致血小板聚集和TxB2完全被抑制。这些结果表明,美洛昔康不影响阿司匹林抑制血小板中COX-1的能力,从而使阿司匹林能够有效预防血小板聚集并降低TxB2水平,且美洛昔康对COX-2具有选择性。