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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 [A U C]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.

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