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Gastric ulcers were produced in male Donryu rats (8-weeks-old) by subserosal injection of 20 microliters of 20% acetic acid. Five days later, an indomethacin (IND)-filled osmotic pump (OP) was implanted into the dorsal subcutaneous space in the rats and maintained for 2, 3 or 4 weeks. The natural healing of the acetic acid-induced ulcers was significantly (P &lt; 0.05) delayed by administration of IND via OP implanted for 4 weeks. Two, 3 and 4 weeks after OP implantation, the plasma IND levels was 1.87 +/- 0.13, 2.43 +/- 0.16 and 0.74 +/- 0.26 (micrograms/ml), respectively, showing that a steady state IND plasma level was maintained for 3 weeks. The gastric mucosal PGE2 levels in rats with ulcers for 3 weeks after implantation of OP were significantly (P &lt; 0.05) reduced by IND (IND(-):576.6 +/- 83.9 pg/mg, IND(+):355.6 +/- 34.7 pg/mg). Repeated administration of enprostil, famotidine and rabeprazole at 25 micrograms/kg, 100 mg/kg and 10 mg/kg (p.o., b.i.d.), respectively, showed anti-ulcer activity. Teprenone and rebamipide had only slight anti-ulcer activity. These findings indicated that this model of delayed healing of acetic acid ulcers by IND using OP is useful for investigating the anti-ulcer activity of drugs.

A new model of delayed healing of acetic acid ulcers in rats by indomethacin via osmotic pump.