Interaction of indomethacin and acetylsalicylic acid as shown by the serum concentrations of indomethacin and salicylate

Abstract

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.