Abstract
Indomethacin is metabolized in humans byO-demethylation, and by acyl glucuronidation to the l-O-glucuronide. Indomethacin, its metabolite, and their conjugates can be measured directly by gradient high-pressure liquid chromatographic analysis without enzymic deglucuronidation. The pharrnacokinetic profile of indomethacin and some preliminary pharmacokinetic parameters of indomethacin obtained from one human volunteer are given. In plasma only the parent drug indomethacin is present, while in urine the acyl and ether glucuronides are present in high concentrations. This confirms other reports that indomethacin andO-desmethylindomethacin may be glucuronidated in the kidney. Probenecid is a known substrate for renal glucuronidation. If indomethacin is glucuronidated in the human kidney like probenecid, then this glucuronidation might be reduced or inhibited under probenecid co-medication. This pilot experiment shows that probenecid reduced the acyl glucuronidation of indomethacin by 50% and completely inhibited the formation ofO-desmethylindomethacin acyl and ether glucuronide.
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Vree, T.B., van den Biggelaar-Martea, M., Verwey-van Wissen, C.P.W.G.M. et al. Probenecid inhibits the glucuronidation of indomethacin andO-desmethylindomethacin in humans. Pharm World Sci 16, 22–26 (1994). https://doi.org/10.1007/BF01870935
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DOI: https://doi.org/10.1007/BF01870935