Summary
The kinetics of a controlled release (CR) formulation of indomethacin 75 mg (Indocid-Retard®) given once daily was compared with a conventional 25 mg indomethacin capsule (Indocid®) given 3 times daily for 7 days, to 14 healthy volunteers, using a randomized, cross-over, multiple-dose study design. The following differences in plasma indomethacin profiles after the 2 treatments were observed: average peak concentrations (Cmax) for the CR regimen were higher and the time to peak (Tmax) was significantly delayed. Trough (pre-morning dose) plasma concentrations (Cmin) on Days 2, 5, 6 and 7 were significantly lower after the CR-formulation. No statistically significant differences between preparations for area under the plasma concentration time curve (AUC0–24h) or for renal clearance were observed. Average steady-state plasma concentrations (C ssp ) on Day 7 of the multiple dose regimens averaged 0.477 and 0.427 µg/ml for the 75 mg CR once daily and the conventional 25 mg t.i.d. treatments, respectively. These results show that the bioavailability of the CR and conventional indomethacin formulations under these multiple-dose conditions was not significantly different.
Similar content being viewed by others
References
Duggan DE, Hogans AF, Kwan FC, McMahon FG (1972) The metabolism of indomethacin in man. J Pharmacol Exp Ther 181: 563–575
Duggan DE, Kwan KC (1979) Enterohepatic recirculation of drugs as a determinant of therapeutic ratio. Drug Metab Rev 9: 21–41
Kwan KC, Breault GO, Umbenhauer ER, McMahon FG, Duggan DE (1976) Kinetics of indomethacin absorption, elimination and enterohepatic circulation in man. J Pharmacokinet Biopharm 6: 255–280
Hucker HB, Zacchei AG, Cox SV, Brodie DA, Cantwell NHR (1966) Studies on the absorption, distribution and excretion of indomethacin in various species. J Pharmacol Exp Ther 153: 237–249
Kwan KC, Bondi JV, Yeh KC (1975) Bioavailability assessment under quasi and non steady-state conditions. I. Theoretical considerations. J Pharm Sci 64: 1639–1642
Wallusch WW, Nowak H, Leopold G, Netter KJ (1978) Comparative bioavailability. Influence of various diets on the bioavailability of indomethacin. Int J Clin Pharmacol 16: 40–44
Fasching U, Eberl R (1978) Vergleich einer neuen Indomethacin-retard Form mit herkömmlichem Indomethacin. Med Wochenschr (Wien) 23: 733–736
Vignon E, Chapuy MC (1979) Biodisponibilité de l'indométhacine. Etude d'une présentation à effet retard. Rev Rheumatol 46: 505–508
Schoog M, Laufen H, Dessain P (1981) A comparison of the pharmacokinetics of piroxicam with those of plain and slow-release indomethacin. Eur J Rheumatol Inflamm 4: 298–302
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Verbesselt, R., Tjandramaga, T.B., Mullie, A. et al. Comparative multiple dose kinetics of two formulations of indomethacin. Eur J Clin Pharmacol 24, 563–568 (1983). https://doi.org/10.1007/BF00609904
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00609904