Gastrointestinal tolerance of [2,2-dimethyl-6-(4-chlorophenyl-7-phenyl- 2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid in the rat.

The gastrointestinal tolerance of [2,2-dimethyl-6-(4-chlorophenyl)-7- phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid (ML 3000, CAS 156897-06-2) has been tested in comparison with indometacin, after both single and multiple administrations for 5 and 11 days in an in vivo rat assay. A single oral administration of ML 3000 at doses of 10, 30 and 100 mg/kg produced no gastrointestinal damage. Repeated oral administration of ML 3000 at daily doses of 10, 30 and 100 mg/kg produced slight gastrointestinal damage, but the effect was minimal and was not found to be statistically significant. Indometacin produced highly statistically significant gastric and duodenal damage following one single administration of 10 mg/kg. Repeated oral administration, at 3 mg/kg each day, produced moderate and statistically significant gastric and slight duodenal damage on Day 5 of dosing. However, by Day 11 pronounced duodenal damage was observed which was shown to be statistically highly significant. These results indicate that ML 3000 is clearly better tolerated by the gastrointestinal tract than indometacin after single and multiple administration up to 11 days in rats.