Kaldestad E, Hansen T, Brath H K
Eur J Clin Pharmacol. 1975 Dec 19;9(2-3):199-207. doi: 10.1007/BF00614018.
A clinical-pharmacological study was performed to determine the effect of acetylsalicylic acid upon the serum concentration of indomethacin. 14 rheumatic patients were given indomethacin orally (25 mg X 4 for 4 days) and concurrently acetylsalicylic acid 3.7 g orally (0.9 g X 3 and 1.0 g X 1 daily), and 21 rheumatic patients were given indomethacin rectally in the morning (100 mg X 1) and concurrently acetylsalicylic acid 3.7 g orally (0.9 g X 3 and 1.0 g X 1 daily). On comparison with treatment with oral or rectal indomethacin alone, it was found that peak serum concentrations of indomethacin were significantly reduced (1% level), the times of the peaks were not shifted, and the areas beneath the serum concentration curves of indomethacin were smaller, but significantly so only if compared with rectal administration. In 12 rheumatic patients given indomethacin by rectum in the evening (100 mg X 1) and concurrently acetylsalicylic acid 3.7 g (0.9 g X 3 and 1.0 g X 1 daily), the serum level of indomethacin on the following morning (after 11 h) did not differ from that found after rectal treatment. A statistically but not biologically significant difference was observed between the mean serum half-lives of indomethacin given orally and rectally. For unknown reasons, concurrent doses of acetylsalicylic acid and indomethacin made the mean serum half-life of indomethacin longer than after its oral administration, but shorter than when the same dose of indomethacin was given rectally. There was no difference between serum levels of salicylate after oral administration of acetylsalicylic acid alone or after a concurrent oral or rectal dose of indomethacin. The results have been related to those reported previously, with respect to the interaction between indomethacin and acetylsalicylic acid, the serum levels of indomethacin after oral and rectal dosing, and the serum half-life of indomethacin based upon a one- or two-compartment model. The clinical relevance of the study is discussed.
进行了一项临床药理学研究，以确定乙酰水杨酸对吲哚美辛血清浓度的影响。14名风湿性疾病患者口服吲哚美辛（25毫克×4，共4天），同时口服乙酰水杨酸3.7克（0.9克×3，1.0克×1，每日一次）；21名风湿性疾病患者于早晨直肠给予吲哚美辛（100毫克×1），同时口服乙酰水杨酸3.7克（0.9克×3，1.0克×1，每日一次）。与单独口服或直肠给予吲哚美辛的治疗相比，发现吲哚美辛的血清峰值浓度显著降低（1%水平），峰值时间未发生偏移，吲哚美辛血清浓度曲线下面积较小，但仅与直肠给药相比时差异有统计学意义。12名风湿性疾病患者于晚上直肠给予吲哚美辛（100毫克×1），同时给予乙酰水杨酸3.7克（0.9克×3，1.0克×1，每日一次），次日早晨（11小时后）吲哚美辛的血清水平与直肠给药后无差异。口服和直肠给予吲哚美辛后的平均血清半衰期之间存在统计学上但无生物学意义的差异。由于未知原因，同时给予乙酰水杨酸和吲哚美辛使吲哚美辛的平均血清半衰期比口服给药后更长，但比直肠给予相同剂量的吲哚美辛时更短。单独口服乙酰水杨酸后或同时口服或直肠给予吲哚美辛后，水杨酸盐的血清水平无差异。已将这些结果与先前报道的关于吲哚美辛与乙酰水杨酸之间的相互作用、口服和直肠给药后吲哚美辛的血清水平以及基于一室或二室模型的吲哚美辛血清半衰期的结果进行了关联。讨论了该研究的临床相关性。
