Aliment Pharmacol Ther 1995: 9: 315-320. zyxwvutsrq Release of 5-ASA from Pentasa in patients with Crohn's disease of the small intestine J. LAROUCHE*, J. MORAIS*, M. PICARD*, C. LAMBERT, J. SPENARD, H. LANDRIAULT, G. KENNEDY z & P. POITRAS* *Hhpital Saint-Luc and Universite' de Montreal, Montreal, Quebec, Canada Accepted for publication 19 January 1995 zyxwvutsrq SUMMARY Background: Pentasa is a controlled-release tablet made from semipermeable microspheres and designed to continuously deliver therapeutic quantities of 5-ASA (5-aminosalicylicacid) throughout the gastrointestinal tract. Scintigraphic studies in healthy subjects have documented that 5-ASA release could occur in the small intestine. We tested here the disintegration of Pentasa in the digestive tract of nine patients with Crohn's disease of the small intestine. Materials: Each patient was given, after breakfast, a 250 mg tablet of Pentasa containing samarium-1 53 oxide. For 8 h the progression of the isotope in the gastrointestinal tract was followed using gamma camera scintigraphy. Plasma measurement of 5-ASA and acetylated 5-ASA was used to verify the liberation and absorption of 5-ASA. Results : The Pentasa tablet appeared completely dissolved in the stomach by 11 7 oxide was first detected in the small intestine 60 zyxw f 5 min after its ingestion : it reached the colon after 280 f 13 min and it was completely absent from the small intestine at 360 f 26 min. Plasma concentrations of 5-ASA started to rise after 67f7minand weremaximalat 222i25min. Conclusion : In patients with Crohn's disease of the small intestine, Pentasa microgranules start releasing 5-ASA in the proximal small intestine, acting locally to exert its beneficial effect. 1 8 min. Samarium INTRODUCTION 5-Aminosalicylicacid (5-ASA)is a well known agent for the treatment of inflammatory bowel disease. Since its beneficial action is exerted topically from the luminal side, different pharmaceutical formulations have been developed to allow orally ingested 5-ASA to reach the inflamed distal intestine without being absorbed in the proximal gut. Salazopyrine is the oldest preparation of 5-ASA; colonic bacteria are able to split the sulfapyri- dine-5-ASA diazo bond to deliver 5-ASA in the large intestine where it can reduce inflammation of ulcerative or granulomatous colitis. Olsalazine is made from two 5-ASA molecules attached by an azo-bond ; this compound is not absorbable by the proximal gut until, in Correspondence to: Dr P. Poitras. Centre de recherche clinique Andre-Viallet, H6pital Saint-Luc, 264 Rene-Livesque Est, Mantrial, Que'bec, Canada, H2X 1 zyxwvutsr P1. the large intestine, colonic bacteria can split and deliver both molecules. Modified release 5-ASA preparations are also available. These formulations use various resins or cellulose products to encapsulate the 5-ASA that will be released along the gastrointestinal tract. For most of these pharmaceutical preparations (Asacol, Salofalk, Mesasal) the 5-ASA is released under the action of pH variation. Pentasa is designed as a tablet or a capsule preparation made from multiple sustained release ethyl- cellulose microgranules. 5-ASA release from the ethyl- cellulose granule formulation of Pentasa is time de- pendent and, in contrast with the other mesalazine preparations, release occurs under all pH conditions. Previous studies have shown that Pentasa can deliver 5-ASA in the small intestine. These studies were per- formed in normal subjects1 or in ileostomy patients having normal small intestinal function.' Pentasa is intended for the treatment of inflammatory lesions of the z 0 1995 Blackwell Science Ltd 315