Systemic availability of 5-aminosalicylic acid: comparison of delayed release and an azo-bond preparation.
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.
Gionchetti
P
P
Instituto di Clinica Medica e Gastroenterologia, University of Bologna, Italy.
Campieri
M
M
Venturi
A
A
Rizzello
F
F
Ferretti
M
M
Brignola
C
C
Miglioli
M
M
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*
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