Effect of pluronic gels on the rectal absorption of indomethacin in rabbits.

Abstract

Indomethacin gel preparations made by dissolving the drug in Pluronic aqueous gels were administered rectally to rabbits and the drug plasma levels were determined. When indomethacin gel preparations with 20% (w/w) Pluronic F-127 were given to rabbits, the plasma concentration reached the maximum level 0.5 h after administration. On the other hand, the 25% (w/w) Pluronic F-127 gel preparation did not show a sharp peak of plasma concentration and produced a sustained-release effect. The 30% (w/w) gel preparation also gave a sustained-release effect, but it was not a desirable preparation because its [AUC] 100 was only half that of a commercial suppository. Pluronic F-108 and Pluronic F-98 did not give a sustained-release effect at the concentration of 25% (w/w).Damage to the mucosal membrane by Pluronic F-127 was rarely found in the rectum. In addition, the individual differences in drug plasma levels following rectal administration of the 25% (w/w) Pluropic F-127 gel preparation were small compared with those of other preparations.These results suggest that the 25% (w/w) Pluronic F-127 gel is most suitable for use as a vehicle for rectal administration of indomethacin with prolonged action and with reduced side effects.