NOVEL TREATMENT OF IRRITABLE BOWEL SYNDROME

The long-term objectives of the proposed research will lead to a clinically useful composition capable of effectively treating certain individuals suffering from irritable bowel syndrome (IBS). The approach involves delivery of a spasmolytic agent to the large intestine using the prodrug approach. The prodrug is poorly absorbed from the upper gastrointestinal tract yet is susceptible to hydrolysis in the colon. There are two specific aims for the proposed research. The first is to examine the pharmacokinetics of delivery of the carminative menthol following intragastric administration of menthol or its glucuronide prodrug; the primary indicator of local cecal and colonic delivery will be the Drug Delivery Index (DDI). The DDI, along with several other pharmacokinetic parameters will be determined by steady-state dosing of the drug or prodrug. The second specific aim will involve studying the efficacy of the prodrug by measuring alterations in overall intestinal transit as measured with a charcoal test meal in the rat (gastric emptying and small intestinal transit) and transit of a class bead to assess colonic transit. The successful outcome of this work will help those individuals suffering from symptoms of IBS.