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Chronopharmacokinetic study of a prolonged release form of indomethacin

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Summary

The chronopharmacokinetics of indomethacin was studied in patients with rheumatoid diseases after a single oral dose of a new prolonged-release form containing indomethacin 75 mg. The drug was given either at 8, 12 or 20 h and its plasma concentrations, as well as those of its main metabolite, O-desmethyl indomethacin, were followed using a new specific gas chromatographic assay. When given at 20 h plasma indomethacin concentrations did not exhibit a sharp peak and remained much more stable than when the drug was given at 8 or 12 h. In addition, plasma O-desmethyl indomethacin was significantly higher after administration of indomethacin at 20 h than at 8 or 12 h. It is concluded that the pharmacokinetics of the oral prolonged-release form of indomethacin exhibited chronobiological variation. The data are in accordance with clinical studies which suggest that it might be worthwhile to administer this formulation of indomethacin at 20 h.

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References

  1. Helleberg L (1981) Clinical pharmacokinetics of indomethacin. Clin Pharmacokinet 6: 245–258

    Google Scholar 

  2. Shen TY (1965) Synthesis and biological activity of some indomethacin analogs. In: Garattini S, Dukes CD (eds) International Symposium on non steroidal anti-inflammatory drugs, International Congress series no 12, Elsevier, Amsterdam, pp 13–20

    Google Scholar 

  3. Clench J, Reinberg A, Dziewenoska Z, Smolensky M (1981) Circadian changes in the bioavailability and effects of indomethacin in healthy subjects. Eur J Clin Pharmacol 20: 359–369

    Google Scholar 

  4. Hollander M, Wolfe DA (1973) Nonparametric statistical methods. J Wiley and Sons, New York, p 144

    Google Scholar 

  5. Reinberg A, Smolensky M (1982) Circadian changes in drug disposition in man. Clin Pharmacokinet 7: 401–420

    Google Scholar 

  6. Kaarela K, Lehtinen K, Mätisara P, Holttinen K, Lamminsivu U, Gordin A (1982) Pharmacokinetics and tolerance of slow-release indomethacin tablets in rheumatoid arthritis. Eur J Clin Pharmacol 23: 349–351

    Google Scholar 

  7. Kwan KC, Breault GO, Umbenhacier ER, Mc Mahon FG, Duggan DE (1975) Kinetics of indomethacin absorption, elimination and enterohepatic circulation in man. J Pharmacokinet Biopharm 4: 255–280

    Google Scholar 

  8. Emori HW, Paulus H, Rodney B, Champion GD, Pearson C (1976) Indomethacin serum concentrations in man. Effects of dosage, food and antacid. Ann Rheum Dis 35: 333–338

    Google Scholar 

  9. Belanger PM, Labrecque G, Dore F (1982) Chronopharmacocinétique des agents anti-inflammatoires non stéroïdiens chez le rat. Tribune Med, no spécial: Chronobiologie, pp 14–21

  10. Zini R, d'Athis P, Barre J, Tillement JP (1979) Binding of indomethacin to human serum-albumin. Its non deplacement by various agents, influence of free-fatty acids and the unexpected effect of indomethacin on warfarin binding. Biochem Pharmacol 28: 2661–2665

    Google Scholar 

  11. Levi F, Le Louarn C, Peltier A (1982) Etude chronothérapeutique en double aveugle de 75 mg d'indomethacine à effet prolongé dans l'arthrose. Tribune Med, no Spécial: Chronobiologie, pp 48–53

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Guissou, P., Cuisinaud, G., Llorca, G. et al. Chronopharmacokinetic study of a prolonged release form of indomethacin. Eur J Clin Pharmacol 24, 667–670 (1983). https://doi.org/10.1007/BF00542219

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  • DOI: https://doi.org/10.1007/BF00542219

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