Pharmaceutisch Weekblad

, Volume 14, Issue 4, pp 191–195 | Cite as

Clearance of indometacin occurs predominantly by renal glucuronidation

  • Frits Moolenaar
  • Sjouke Crancrinus
  • Jan Visser
  • Dick De Zeeuw
  • Dirk K. F. Meijer


In this report we describe the conditions of collection, storage and handling of urine samples, collected after oral dosing with indometacin in man, in order to maintain the integrity of the labile glucuronide formed. We found that the body clearance occurs predominantly by renal metabolism, due to glucuronidation in the human kidney. These glucuronides may be converted to isomeric glucuronides and/or the parent compound indometacin during the residence time in the bladder.


Clearance, metabolic Clearance, renal Glucuronates Indometacin Pharmacokinetics 


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  1. 1.
    Dick WC. Drug treatment of rheumatoid arthritis. In: Scott JR, ed. Copeman's textbook of the rheumatic diseases. 5th ed. New York: Churchill Livingstone, 1978:404–46.Google Scholar
  2. 2.
    Duggan DE, Hogans AF, Kwan KC, McMahon FG. The metabolism of indomethacin in man. J Pharmacol Exp Ther 1972;181:563–75.PubMedGoogle Scholar
  3. 3.
    Helleberg L. Clinical pharmacokinetics of indomethacin. Clin Pharmacokinet 1981;6:245–58.PubMedGoogle Scholar
  4. 4.
    Kwan KC, Breault GO, Umbenbauer ER, McMahon FG, Duggan DE. Kinetics of indomethacin absorption, elimination and enterohepatic circulation in man. J Pharmacokinet Biopharm 1976;4:255–80.PubMedGoogle Scholar
  5. 5.
    Woodhouse KW, Wynne H. The pharmacokinetics of non-steroidal anti-inflammatory drugs in the eldery. Clin Pharmacokinet 1987;12:111–22.PubMedGoogle Scholar
  6. 6.
    Verbeeck RK. Pharmacokinetic drug interactions with nonsteroidal anti-inflammatory drugs. Clin Pharmacokinet 1990;19:44–66.PubMedGoogle Scholar
  7. 7.
    Faed EM. Properties of acyl glucuronides:implications for studies of the pharmacokinetics and metabolism of acidic drugs. Drug Metab Rev 1984;15:1213–49.PubMedGoogle Scholar
  8. 8.
    Sinclair KA, Caldwell J. The formation ofβ-glucuronidase resistant glucuronides by the intramolecular rearrangement of glucuronic acid conjugates at mild alkaline pH. Biochem Pharmacol 1982;13:953–7.Google Scholar
  9. 9.
    Smith PC, Hasegawa J, Langendijk PNJ, Benet LZ. Stability of acyl glucuronides in blood, plasma, and urine. Studies with zomepirac. Drug Metab Dispos 1985;13:110–2.PubMedGoogle Scholar
  10. 10.
    Hasegawa J, Smith PC, Benet LZ. Apparent intramolecular acyl migration of zomepirac glucuronide. Drug Metab Dispos 1982;10:469–73.PubMedGoogle Scholar
  11. 11.
    Galeazzi RL. The effect of antacid on the bioavailability of indomethacin. Eur J Clin Pharmacol 1977;12:65–8.PubMedGoogle Scholar
  12. 12.
    Baber N, Halliday L, Sibeon R, Littler T, Orme MLE. The interaction between indomethacin and probenecid. Clin Pharmacol Ther 1978;24:299–307.Google Scholar
  13. 13.
    Terhaag B, Hermann U. Biliary elimination of indomethacin in man. Eur J Clin Pharmacol 1986;29:691–5.PubMedGoogle Scholar
  14. 14.
    Hucker HB, Zacchei AG, Cox SV, Brodie DA, Cantwell NHR. Studies on the absorption, distribution and excretion of indomethacin in various species. J Pharmacol Exp Ther 1966;153:237–49.Google Scholar
  15. 15.
    Harman RE, Meisinger MAP, Davis GE, Kuehl FA. The metabolites of indomethacin, a new antiinflammatory drug. J Pharmacol Exp Ther 1964;143:215–20.PubMedGoogle Scholar
  16. 16.
    Vree TB, Beneken Kolmer EWJ, Hekster YA. Pharmacokinetics, N1-glucuronidation and N4-acetylation of sulfamethomidine in humans. Pharm Weekbl [Sci] 1991;13(5):198–206.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1992

Authors and Affiliations

  • Frits Moolenaar
    • 1
  • Sjouke Crancrinus
    • 2
  • Jan Visser
    • 1
  • Dick De Zeeuw
    • 3
  • Dirk K. F. Meijer
    • 1
  1. 1.Department of Pharmacology and TherapeuticsUniversity Centre for PharmacyAW Groningenthe Netherlands
  2. 2.Pharmacy Huis te LandeVJ Rijswijkthe Netherlands
  3. 3.Department of NephrologyUniversity Hospital GroningenRB Groningenthe Netherlands

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