Comparative multiple dose kinetics of two formulations of indomethacin.

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 (AUC0-24 h) or for renal clearance were observed. Average steady-state plasma concentrations (Cssp) on Day 7 of the multiple dose regimens averaged 0.477 and 0.427 microgram/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.

RCT Entities:   Population Interventions Outcomes