Cibattoni G, Boss A H, Patrignani P, Catella F, Simonetti B M, Pierucci A, Pugliese F, Filabozzi P, Patrono C
Clin Pharmacol Ther. 1987 Apr;41(4):380-3. doi: 10.1038/clpt.1987.44.
We measured the renal and extrarenal synthesis of prostacyclin and thromboxane A2, as reflected by the urinary excretion of the stable hydration products 6-keto-prostaglandin F 1 alpha and thromboxane B2 and the corresponding 2,3-dinor-derivatives, during chronic administration of sulindac (200, 400, 600, and 800 mg/day, each dose given for 7 days in successive weeks) in seven healthy subjects. Urinary eicosanoids were measured by negative ion, chemical ionization-GC/MS-validated RIA techniques. Both 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F 1 alpha showed a dose-dependent reduction, ranging between 45% and 85%. In contrast, the urinary excretion of 6-keto-prostaglandin F1 alpha and thromboxane B2 did not change significantly throughout the study. These results extend previous observations of a selective sparing of renal cyclooxygenase activity by sulindac in humans and demonstrate that this selectivity is not related to an overall weaker enzyme inhibition.
我们在7名健康受试者中，通过稳定水合产物6-酮-前列腺素F1α和血栓素B2以及相应的2,3-二去甲衍生物的尿排泄量，来测定前列腺素I2和血栓素A2的肾内和肾外合成，这些受试者连续数周每天服用舒林酸（200、400、600和800毫克，每个剂量服用7天）。通过负离子、化学电离-气相色谱/质谱验证的放射免疫分析技术测定尿类花生酸。2,3-二去甲血栓素B2和2,3-二去甲-6-酮-前列腺素F1α均呈剂量依赖性降低，降低幅度在45%至85%之间。相比之下，在整个研究过程中，6-酮-前列腺素F1α和血栓素B2的尿排泄量没有显著变化。这些结果扩展了之前关于舒林酸对人体肾环氧化酶活性有选择性保留作用的观察，并表明这种选择性与整体较弱的酶抑制作用无关。
