title: Systemic availability of 5-aminosalicylic acid: comparison of delayed release and an azo-bond preparation.
abstract: OBJECTIVE
  To determine the systemic uptake of 5-aminosalicylic acid (5-ASA) and acetyl-5-ASA (Ac-5-ASA) at steady state during treatment with either an azo-bond preparation, olsalazine, or a delayed-release mesalazine.
  
  
  METHODS
  In an open cross-over trial with randomized sequence, 15 patients with ulcerative colitis in remission were given 7-day courses of olsalazine (Dipentum 1.0 g daily) and of mesalazine (Asacol 1.6 g daily). Plasma and urine were collected on days 6 and 7 of each course and concentrations of 5-ASA and Ac-5-ASA were determined by high-performance liquid chromatography (HPLC).
  
  
  RESULTS
  Mean steady-state plasma concentrations of 5-ASA and Ac-5-ASA were significantly higher after treatment with mesalazine than with olsalazine (P < 0.0001). Total urinary excretion of 5-ASA and Ac-5-ASA as a percentage of the given dose was significantly higher on mesalazine than on olsalazine (P < 0.01). Only two patients experienced, during the first 3 days of treatment with olsalazine, transient watery diarrhoea which resolved spontaneously. No unexpected or major changes in haematology or biochemistry were detected during the study.
  
  
  CONCLUSIONS
  As 5-ASA acts locally, the lower systemic load provided by olsalazine may increase efficacy and reduce the potential risk of nephrotoxicity during long-term maintenance treatment of ulcerative colitis.
authors.affiliation: Instituto di Clinica Medica e Gastroenterologia, University of Bologna, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Gionchetti
authors.forename: M
authors.initials: M
authors.lastname: Campieri
authors.forename: A
authors.initials: A
authors.lastname: Venturi
authors.forename: F
authors.initials: F
authors.lastname: Rizzello
authors.forename: M
authors.initials: M
authors.lastname: Ferretti
authors.forename: C
authors.initials: C
authors.lastname: Brignola
authors.forename: M
authors.initials: M
authors.lastname: Miglioli
mesh_terms: D000328:Adult; D000368:Aged; D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D003093:Colitis, Ulcerative / Q000188:drug therapy; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D019804:Mesalamine; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D011355:Prodrugs; D019804:Mesalamine; C028836:N-acetyl-5-aminosalicylic acid; C032587:olsalazine