Gastrointestinal transit and 5‐ASA release from a new mesalazine extended‐release formulation

Summary Background : Mesalazine (5‐aminosalicylic acid, 5‐ASA)‐containing formulations represent a cornerstone in the treatment of inflammatory bowel diseases. Recently, a new formulation has been developed to provide selective and more homogeneous release of 5‐ASA compared to traditional systems. Methods : In a first study, gastrointestinal transit was followed by gamma‐scintigraphy after single‐dose application of tablets containing 1200 mg mesalazine to 12 healthy male volunteers. 5‐ASA release was verified by the assessment of plasma pharmacokinetics. In a second, 7‐day, multiple‐dose study, the steady state plasma pharmacokinetics, urinary excretion and safety profile were characterized after twice‐daily tablet administration to 12 healthy volunteers. Results : Tablet erosion started after 6.9 ± 1.1 h in the ascending or transverse colon. Radioactivity spread homogeneously throughout the colon, indicating the sustained release of active 5‐ASA. Plasma kinetics indicated an earlier initial absorption of 5‐ASA, i.e. during transit of the small intestine and ileum. Mean Cmax values (350.6 ± 322.6 ng/mL) were observed during location in the ileo‐caecal region. The mean relative absorption of 5‐ASA was 19.9 ± 18.2% in the small intestine and ileum and 80.1 ± 18.2% in the colon. Conclusions : The administration of the new mesalazine formulation was well tolerated, and 5‐ASA was continuously released along the whole colon, a favourable prerequisite for the therapy of distally located inflammatory bowel disease.