Stereoselective disposition of sustained release microspheres of ibuprofen enantiomers in rats: II. Acute gastrointestinal toxicity

Abstract

The purpose of this study was to examine acute gastrointestinal tract (GIT) toxicity caused by the pure enantiomers of ibuprofen in male Wistar rats. A 2x2x2 factorial design in which rats were randomly divided into eight experimental groups and a control group was used. They were dosed with the sustained release microsphere and conventional suspensions of ibuprofen enantiomers at 20 mg/kg and 40 mg/kg dose levels. Bethanechol chloride (5 mg/kg), a cholinomimetic agent, was administered 30 min after dosing to induce gastric irritation. Animals were euthanized at different time intervals up to 48 hr postdosing followed by excision of stomach and intestinal tract. Blood samples also were collected during this study by cardiac puncture and stereospecifically analyzed. Tissues were examined for lesions and hemorrhages macroscopically (x75 magnification) using top and bottom illumination. Macroscopic evaluation of the tissue samples revealed significant differences in the GIT toxicity caused by S- and R-ibuprofen at the 40 mg/kg level (p