Kwan K C, Breault G O, Davis R L, Lei B W, Czerwinski A W, Besselaar G H, Duggan D E
J Pharmacokinet Biopharm. 1978 Dec;6(6):451-76. doi: 10.1007/BF01062103.
Ten healthy volunteers each received single and multiple 50-mg doses of indomethacin orally and a single 25-mg dose of [14C]indomethacin intravenously in the absence of and concomitantly with 1200 mg of aspirin as a single dose and in a chronic t.i.d. regimen. Systematic analysis of the data resulted in the isolation and quantification of aspirin's effects on the absorption, distribution, biotransformation, excretion, enterohepatic circulation, and accumulation of indomethacin. The effects of chronic aspirin were to suppress the renal clearance, to increase the biliary clearance, to decrease the efficiency of gastrointestinal absorption, and to enhance the enterohepatic circulation of indomethacin. On concomitant administration of 1200 mg of aspirin t.i.d., mean plasma levels of indomethacin were depressed by 20% after a single oral dose, by a smaller margin after multiple oral doses, and not at all after a single intravenous dose of indomethacin. The mean plasma concentration of orally administered indomethacin was decreased by 8% when given concurrently with a single 1200 mg dose of aspirin. Concomitant chronic therapeutic dosages of indomethacin had no effect on salicylate accumulation from repetitive doses of aspirin.
10名健康志愿者分别单次和多次口服50毫克吲哚美辛，并在单次服用1200毫克阿司匹林以及慢性每日三次服用该剂量阿司匹林的情况下，静脉注射单次25毫克剂量的[14C]吲哚美辛。对数据进行系统分析后，分离并量化了阿司匹林对吲哚美辛的吸收、分布、生物转化、排泄、肠肝循环及蓄积的影响。长期服用阿司匹林的影响包括抑制肾清除率、增加胆汁清除率、降低胃肠道吸收效率以及增强吲哚美辛的肠肝循环。每日三次服用1200毫克阿司匹林时，单次口服吲哚美辛后，吲哚美辛的平均血浆水平降低20%，多次口服后降低幅度较小，而静脉注射单次剂量吲哚美辛后则无影响。与单次1200毫克剂量阿司匹林同时服用时，口服吲哚美辛的平均血浆浓度降低8%。同时服用长期治疗剂量的吲哚美辛对重复服用阿司匹林后的水杨酸盐蓄积无影响。
