Oral mesalazine for the treatment of Crohn's disease: clinical efficacy with respect to pharmacokinetic properties.

The release of 5-ASA from various preparations depends on the presence of bacterial azoreductases (sulphasalazine, olsalazine, balsalazide) or the pharmacokinetic properties of the mesalazine-containing pharmaceutical preparations. The differences of the 5-ASA release from the various preparations account for the different anatomic sites of actions. In this regard, a close relationship between the regional intraluminal concentrations of 5-ASA and the clinical response can be assumed. The aim of the present paper is to survey clinical trials in Crohn's disease with special respect to the pharmacokinetic properties of the used mesalazine containing preparations. There are clear differences between the different coated 5-ASA formulas in respect to 5-ASA release and in respect to their pharmacokinetic properties leading to a different therapeutic efficacy in Crohn's disease. The detailed analysis indicates that higher doses of 5-ASA (> 3 g/d) are required for the acute phase treatment. 4.5 g Eudragit-L-coated 5-ASA tablets are almost equally as potent as glucocorticosteroids for the treatment of active Crohn's disease. Clinical efficacy has been demonstrated for Eudragit-L-coated tablets even at a low dose of 1-1.5 g 5-ASA/day in the maintenance treatment of remission of Crohn's disease. This has also been shown for Eudragit-S-coated tablets at a dose of 2.4 g 5-ASA/day, while even 3 g 5-ASA of an Eudragit-L/S formula as well as the ethylcellulose-coated formulas up to 4 g 5-ASA/day were ineffective, except for a high risk group. On the basis of the published trials, there is clear evidence that post-operative prophylaxis with 5-ASA requires daily doses higher than 1.5 g. Ethylcellulose-coated 5-ASA has only been effective in Crohn's disease limited to the small bowel and should not be given to patients with ileo-colonic or colonic disease. Moreover, Eudragit-L-coated 5-ASA preparations have shown to be effective in both ileal and colonic disease concerning their clinical efficacy in post-operative prophylaxis. In contrast, endoscopic efficacy has been demonstrated for ethylcellulose as well as Eudragit-S-coated formulas. Treatment of Crohn's disease with orally administered 5-ASA can generally be regarded as an effective and well-tolerated therapy. However, the distinct therapeutic goal (acute phase treatment, maintenance therapy or post-operative prophylaxis), the involved areas of the gut and the specific release of the drug administered have to be considered.