Stichtenoth D O, Wagner B, Frölich J C
Institute of Clinical Pharmacology, Hannover Medical School, Germany.
J Investig Med. 1997 Feb;45(2):44-9.
Meloxicam is a new NSAID with selectivity for the inducible cyclooxygenase (COX-2) in vitro. We compared the effects of therapeutically equivalent doses of meloxicam and indomethacin, a preferential inhibitor of the constitutive cyclooxygenase (COX-1), on platelet aggregation and platelet thromboxane formation, which are exclusively COX-1 dependent, physiological renal, and total body prostaglandin E2 (PGE2) production.
In a randomized cross-over design, 14 healthy female volunteers received meloxicam 7.5 mg per day for 6 days or indomethacin 25 mg three times per day for 3 days; the wash-out period was 5 days, and drug intake was adapted to the menstrual cycle. On the day before treatment and on the last day of each treatment period the following parameters were evaluated: maximum platelet aggregation and thromboxane B2 (TXB2) formation in response to 1.0 mmol/L arachidonic acid; 24-hour urinary excretion of PGE2 and 7 alpha-hydroxy-5, 11-diketo-tetranor-prosta-1, 16-dionic acid (PGE-M), the index metabolites of renal and total body PGE2 synthesis, respectively, were assessed by gas chromatography/tandem mass spectrometry.
Maximum platelet aggregation and TXB2 formation were almost completely inhibited by indomethacin (-87% and -99%, respectively; p < 0.001, each) as compared to control (100%), but remained unaffected by meloxicam (-1% and +4%, respectively). Meloxicam showed no significant effects on urinary PGE2 excretion (-13%) and only slight effects on PGE-M excretion (-22%; p < 0.05), whereas indomethacin reduced urinary PGE2 excretion (-43%; p < 0.05) as well as PGE-M excretion (-36%; p < 0.001).
Our data show, that meloxicam 7.5 mg per day is COX-1 sparing in humans in vivo.
美洛昔康是一种新型非甾体抗炎药，在体外对诱导型环氧化酶（COX-2）具有选择性。我们比较了治疗等效剂量的美洛昔康和吲哚美辛（一种组成型环氧化酶（COX-1）的优先抑制剂）对血小板聚集和血小板血栓素形成的影响，血小板聚集和血小板血栓素形成完全依赖于COX-1，还比较了它们对生理性肾和全身前列腺素E2（PGE2）生成的影响。
采用随机交叉设计，14名健康女性志愿者每天服用7.5毫克美洛昔康，共6天，或每天服用25毫克吲哚美辛，分三次服用，共3天；洗脱期为5天，药物摄入根据月经周期进行调整。在治疗前一天和每个治疗期的最后一天，评估以下参数：对1.0毫摩尔/升花生四烯酸的最大血小板聚集和血栓素B2（TXB2）形成；通过气相色谱/串联质谱法评估PGE2的24小时尿排泄量以及7α-羟基-5,11-二酮-四降-前列腺-1,16-二酸（PGE-M），分别为肾和全身PGE2合成的指标代谢物。
与对照组（100%）相比，吲哚美辛几乎完全抑制了最大血小板聚集和TXB2形成（分别为-87%和-99%；p<0.001），但美洛昔康对其无影响（分别为-1%和+4%）。美洛昔康对尿PGE2排泄无显著影响（-13%），对PGE-M排泄仅有轻微影响（-22%；p<0.05），而吲哚美辛降低了尿PGE2排泄（-43%；p<０.05）以及PGE-M排泄（-36%；p<0.001）。
我们的数据表明，每天7.5毫克的美洛昔康在人体内对COX-1具有保护作用。
