N Bodor1, T Murakami, W M Wu. 1. Center for Drug Discovery, J. Hillis Miller Health Center, College of Pharmacy, University of Florida, Gainesville 32610, USA.
Abstract
PURPOSE: As a safe anti-inflammatory corticosteroid, the utility of loteprednol etabonate (LE) for the treatment of gastrointestinal inflammation, via oral and rectal administration, was investigated in rats. METHODS: In vivo, LE solution and suspension were orally administered (20 mg/kg), and various LE preparations (solution, suspension & suppository) were applied in rectal loops (0.2 mg per loop). In vitro, various GI tissues were used to study the stability and partition of LE. RESULTS: After oral administration of LE solution, LE reached the upper GI tract effectively, but not the colon, due to absorption and/or decomposition. In suspension, LE reached most of the GI tract (except rectum) in 8 hr and showed little absorption. After rectal applications, LE remained intact in the rectal loop for more than five hours with a slow rate of disappearance, however, LE distributed in the rectal membrane to some extent. The concentrations of LE and its inactive metabolites in plasma after both oral and rectal administrations were lower than the detection limit (0.1 microgram/ml) at anytime during the experiments. In vitro, LE in solution was stable in stomach, but not in cecum, due to the hydrolysis by the cecal resident micro flora. In solution, LE distributed into the mucosal membranes efficiently (about 2.5-4.0 micrograms/g tissue). CONCLUSIONS: The results suggest that LE can be orally or rectally delivered in the GI tract for the topical treatment of the inflammatory bowel disease.
PURPOSE: As a safe anti-inflammatory corticosteroid, the utility of loteprednol etabonate (LE) for the treatment of gastrointestinal inflammation, via oral and rectal administration, was investigated in rats. METHODS: In vivo, LE solution and suspension were orally administered (20 mg/kg), and various LE preparations (solution, suspension & suppository) were applied in rectal loops (0.2 mg per loop). In vitro, various GI tissues were used to study the stability and partition of LE. RESULTS: After oral administration of LE solution, LE reached the upper GI tract effectively, but not the colon, due to absorption and/or decomposition. In suspension, LE reached most of the GI tract (except rectum) in 8 hr and showed little absorption. After rectal applications, LE remained intact in the rectal loop for more than five hours with a slow rate of disappearance, however, LE distributed in the rectal membrane to some extent. The concentrations of LE and its inactive metabolites in plasma after both oral and rectal administrations were lower than the detection limit (0.1 microgram/ml) at anytime during the experiments. In vitro, LE in solution was stable in stomach, but not in cecum, due to the hydrolysis by the cecal resident micro flora. In solution, LE distributed into the mucosal membranes efficiently (about 2.5-4.0 micrograms/g tissue). CONCLUSIONS: The results suggest that LE can be orally or rectally delivered in the GI tract for the topical treatment of the inflammatory bowel disease.