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 b acterial azoreductases (sulphasalazine, olsalazine, balsalazide) or the pha rmacokinetic properties of the mesalazine-containing pharmaceutical prepara tions. The differences of the 5-ASA release from the various preparations a ccount 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 s urvey clinical trials in Crohn's disease with special respect to the pharma cokinetic 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 detail ed analysis indicates that higher doses of 5-ASA (>3g/d) are required for t he acute phase treatment. 4.5g Eudragit-L-coated 5-ASA tablets are almost e qually as potent as glucocorticosteroids for the treatment of active Crohn' s disease. Clinical efficacy has been demonstrated for Eudragit-L-coated ta blets even at a low dose of 1-1.5g 5-ASA/day in the maintenance treatment o f remission of Crohn's disease. This has also been shown for Eudragit-S-coa ted tablets at a dose of 2.4g 5-ASA/day, while even 3g 5-ASA of an Eudragit -L/S formula as well as the ethylcellulose-coated formulas up to 4g 5-ASA/d ay were ineffective, except for a high risk group. On the basis of the publ ished trials, there is clear evidence that post-operative prophylaxis with 5-ASA requires daily doses higher than 1.5g. Ethylcellulose-coated 5-ASA ha s only been effective in Crohn's disease limited to the small bowel and sho uld 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 i leal and colonic disease concerning their clinical efficacy in post-operati ve 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 effe ctive and well-tolerated therapy. However, the distinct therapeutic goal (a cute phase treatment, maintenance therapy or post-operative prophylaxis), t he involved areas of the gut and the specific release of the drug administe red have to be considered.