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  • Title: Determination of indomethacin, its metabolites and their glucuronides in human plasma and urine by means of direct gradient high-performance liquid chromatographic analysis. Preliminary pharmacokinetics and effect of probenecid.
    Author: Vree TB, van den Biggelaar-Martea M, Verwey-van Wissen CP.
    Journal: J Chromatogr; 1993 Jul 02; 616(2):271-82. PubMed ID: 8376508.
    Abstract:
    Indomethacin is metabolized in humans by O-demethylation, and by acyl glucuronidation to the 1-O-glucuronide. Indomethacin, its metabolite O-desmethylindomethacin (DMI) and their conjugates can be measured directly by gradient high-performance liquid chromatographic analysis without enzymic deglucuronidation. The glucuronide conjugates were isolated by preparative HPLC from human urine samples. In plasma only indomethacin was present. No isoglucuronides were present in acidic urine of the volunteer. The possible metabolite deschlorobenzoylindomethacin (DBI) was not detectable in urine. Calibration curves were constructed by enzymic deconjugation of samples containing different concentrations of isolated indomethacin acyl glucuronide, DMI acyl glucuronide and DMI ether glucuronide. The limit of quantitation of indomethacin in plasma is 0.060 microgram/ml. The limits of quantitation in urine are: indomethacin 0.053 microgram/ml, DMI 0.065 microgram/ml, DMI acyl glucuronide 0.065 microgram/ml and DMI ether glucuronide 0.254 microgram/ml. A pharmacokinetic profile of indomethacin is shown, and some preliminary pharmacokinetic parameters of indomethacin obtained from one human volunteer are given. Probenecid inhibits the formation of both the ether and the acyl glucuronide of DMI.
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