Stichtenoth D O, Tsikas D, Gutzki F M, Frölich J C
Institute of Clinical Pharmacology, Hannover Medical School, Germany.
Eur J Clin Pharmacol. 1996;51(3-4):231-4. doi: 10.1007/s002280050189.
In the present randomized, fourway crossover study we determined the effects of two oral doses each of ketoprofen and ibuprofen on platelet aggregation and prostanoid formation in man.
Twelve healthy female volunteers received for 2 consecutive days, followed by a 5-day drug-free interval, one of the following: ketoprofen 3 x 25 mg per day, or ketoprofen 3 x 50 mg per day, or ibuprofen 3 x 200 mg per day, or ibuprofen 3 x 400 mg per day. The response criteria, determined before and on the 2nd day of each treatment period, were: maximal platelet aggregation in response to 1.0 mmol.l-1 arachidonic acid measured by the method of Born and Cross, thromboxane B2 (TXB2) concentration in platelet-rich plasma after aggregation measured by radioimmunoassay, and PGE-M, the index metabolite of total body prostaglandin E2 (PGE2) production, assessed by gas chromatography/tandem mass spectrometry using 18O2-PGE-M as internal standard.
Platelet aggregation was significantly reduced by ketoprofen 3 x 25 mg per day (-57%) and ketoprofen 3 x 50 mg per day (-85%) as compared to control, whereas ibuprofen 3 x 200 mg per day (-3%) and ibuprofen 3 x 400 mg per day (-22%) had no significant effects. TXB2 synthesis was significantly decreased by ketoprofen 3 x 25 mg per day (-72%), ketoprofen 3 x 50 mg per day (-97%) and ibuprofen 3 x 400 mg per day (-48%) as compared to control; ibuprofen 3 x 200 mg per day did not reduce TXB2 formation significantly (-23%). All four treatments reduced 24-h urinary excretion of PGE-M significantly in the range of -39% (ketoprofen 3 x 25 mg per day) to -53% (ibuprofen 3 x 400 mg per day) without significant differences between treatments.
Our data show that both ketoprofen dosages were more effective in inhibition of platelet aggregation and platelet thromboxane synthesis than ibuprofen in low or high dosage. Total body synthesis of the E-prostaglandins was inhibited by all drug schedules without significant differences between treatments.
在本随机、四交叉研究中，我们确定了酮洛芬和布洛芬的两种口服剂量对人体血小板聚集和前列腺素生成的影响。
12名健康女性志愿者连续2天接受以下治疗之一，随后为5天的无药间隔期：酮洛芬每日3次，每次25mg；或酮洛芬每日3次，每次50mg；或布洛芬每日3次，每次200mg；或布洛芬每日3次，每次400mg。在每个治疗期的第1天和第2天之前测定的反应标准为：采用Born和Cross方法测定对1.0mmol.l-1花生四烯酸的最大血小板聚集率；采用放射免疫分析法测定聚集后富血小板血浆中血栓素B2（TXB2）浓度；采用气相色谱/串联质谱法，以18O2-PGE-M作为内标，评估全身前列腺素E2（PGE2）生成的指标代谢物PGE-M。
与对照组相比，酮洛芬每日3次，每次25mg（-57%）和酮洛芬每日3次，每次50mg（-85%）可显著降低血小板聚集率，而布洛芬每日3次，每次200mg（-3%）和布洛芬每日3次，每次400mg（-22%）无显著影响。与对照组相比，酮洛芬每日3次，每次25mg（-72%）、酮洛芬每日3次，每次50mg（-97%）和布洛芬每日3次，每次400mg（-48%）可显著降低TXB2合成；布洛芬每日3次，每次200mg对TXB2生成的降低作用不显著（-23%）。所有四种治疗均显著降低了PGE-M的24小时尿排泄量，范围为-39%（酮洛芬每日3次，每次25mg）至-53%（布洛芬每日3次，每次400mg），各治疗组之间无显著差异。
我们的数据表明，两种剂量的酮洛芬在抑制血小板聚集和血小板血栓素合成方面比低剂量或高剂量的布洛芬更有效。所有药物方案均抑制了E-前列腺素的全身合成，各治疗组之间无显著差异。
