Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Layer, P.H. et al.

Delivery and fate of oral mesalamine microgranules within the human small intestine.

BACKGROUND/AIMS: Oral use of mesalamine in inflammatory bowel disease requires slow-release preparations to prevent premature absorption and inactivation. Resulting luminal concentrations within the human small intestine are unknown. The aim of this study was to determine human intestinal delivery patterns of mesalamine from a microgranule preparation (Pentasa; Ferring Arzeimittel, Kiel, Germany) effective in Crohn's disease with small bowel involvement. METHODS: A multilumen tube for duodenal, jejunal, and ileal aspiration and marker perfusion was placed in 6 normal subjects. Levels of luminal, plasma, and urinary mesalamine and its main metabolite, acetyl mesalamine, were measured for 7 hours after ingestion of mesalamine (500 mg) with a labeled meal. RESULTS: Gastric emptying of mesalamine paralleled the meal, and its release occurred throughout the small intestine (cumulative, 20% of dose). For 4 hours, mean luminal mesalamine and acetyl mesalamine concentrations were 52 and 38 micrograms/mL (duodenum), 59 and 82 micrograms/mL (jejunum), and 64 and 104 micrograms/mL (ileum). Cumulative colonic delivery was 82% (7% dissolved, 75% in microgranules), and urinary excretion was 3.5%. CONCLUSIONS: Although the major part of continuous-release mesalamine is delivered to the colon, large proportions are liberated and available at high concentrations within the small intestinal lumen, thus explaining its therapeutic efficacy in small intestinal Crohn's disease.[1]

References

Delivery and fate of oral mesalamine microgranules within the human small intestine. Layer, P.H., Goebell, H., Keller, J., Dignass, A., Klotz, U. Gastroenterology (1995) [Pubmed]

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