Systemic uptake of 5-aminosalicylic acid from olsalazine and eudragit L coated mesalazine in patients with ulcerative colitis in remission.
Aminosalicylates are used to maintain remission in patients with ulcerative colitis. Since there are potential systemic side effects of 5-aminosalicylic acid (5-ASA) and long term treatment is necessary for maintenance therapy preparations with low rates of absorption in the small intestine would be optimal for this indication. In this trial olsalazine (Dipentum), a 5-ASA dimer, and an eudragit L coated mesalazine preparation (Salofalk) were compared.


METHODS
Fifteen patients with ulcerative colitis in clinical and endoscopical remission were randomized in a cross over design. They either received a 2 x 2 capsules of olsalazine 250 mg or 3 x 2 tablets mesalazine 250 mg, these being the doses recommended for maintenance therapy. After a five days equilibration period morning pre-dose serum samples and 24 hour urine were collected on two consecutive days and analyzed for 5-ASA and acetylated 5-ASA. Subsequently, patients were crossed over to receive the alternative preparation and were evaluated after five days correspondingly.


RESULTS
Uptake of 5-ASA from mesalazine was significantly higher than from olsalazine (p < 0.0001). Plasma concentrations of 5-ASA were 3.4 times and of acetyl-5-ASA 3.2 times higher after mesalazine administration than after olsalazine. The same applies to the 24 hour 5-ASA and acetyl-5-ASA urinary excretion (median: 3.2 versus 1.0 mmol/24 hr) as well as to the percentage of administered dose (32.4 versus 17.7%). All patients finished the trial and no major systemic side effects occured with either preparation.


CONCLUSIONS
Systemic uptake of 5-ASA from olsalazine was significantly lower than from eudragit L coated mesalazine. Therefore, olsalazine is less likely to produce side effects and seems to be especially suited for maintenance therapy in ulcerative colitis.
Ewe
K
K
Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität Mainz.
Becker
K
K
Ueberschaer
B
B
D000328:Adult; D000368:Aged; D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001711:Biotransformation; D003093:Colitis, Ulcerative / Q000097:blood* / Q000188:drug therapy; D003289:Convalescence; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D019804:Mesalamine; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D019804:Mesalamine; C032587:olsalazine