Dell H D, Doersing M, Fischer W, Jacobi H, Kamp R, Köhler G, Schöllnhammer G
Arzneimittelforschung. 1980;30(8A):1391-8.
Metabolism and pharmacokinetics of [1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy]-acetic acid (acemetacin, TV 1322, Rantudil) in comparison to equimolar doses of indometacin was investigated in human volunteers after a single oral application and in rheumatic patients after multiple application. After multiple application (t.i.d. for 10 days) of equimolar doses of acemetacin and indometacin, mean blood level curves. The bioavailability of acemetacin derived from these data, corresponds to that of indometacin, i.e., approx. 100%, whereas after a single dose bioavailability of acemetcin is found to be smaller (66% from blood level, 64% from urine). This difference between single and multiple application is explained by slow filling-up of compartments. Degradation of acemetacin occurs by esterolytic cleavage to indometacin, by O-demethylation and N-desacylation and by partial conjugation of all these compounds to glucuronic acid. Blood level ratios of acemetacin and indometacin are equal after single and after multiple application of acemetacin. Therefore, degradation of acemetacin is not induced after multiple application. After a steady-state has been reached half-life of elimination is 4.5 +/- 2.8 h, which is longer than for indometacin (2.2 +/- 0.5 h). Interindividual differences are in the same range as described for indometacin.
在人类志愿者单次口服给药后以及风湿性疾病患者多次给药后，对[1-(对氯苯甲酰基)-5-甲氧基-2-甲基吲哚-3-乙酰氧基]乙酸（阿西美辛，TV 1322，炎痛新）与等摩尔剂量吲哚美辛的代谢和药代动力学进行了研究。在多次给予等摩尔剂量的阿西美辛和吲哚美辛（每日3次，共10天）后，平均血药浓度曲线……从这些数据得出的阿西美辛的生物利用度与吲哚美辛相当，即约为100%，而单次给药后阿西美辛的生物利用度较小（血药浓度测定为66%，尿药测定为64%）。单次和多次给药之间的这种差异可以用房室缓慢充盈来解释。阿西美辛通过酯解裂解为吲哚美辛、O-去甲基化和N-去酰化以及所有这些化合物与葡萄糖醛酸的部分结合而发生降解。单次和多次给予阿西美辛后，阿西美辛与吲哚美辛的血药浓度比相等。因此，多次给药后不会诱导阿西美辛的降解。达到稳态后，消除半衰期为4.5±2.8小时，比吲哚美辛（2.2±0.5小时）长。个体间差异与吲哚美辛描述的范围相同。 （注：原文中“mean blood level curves.”之后内容缺失）
