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.