Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion.
To compare the disposition of 5-aminosalicylic acid (5-ASA) and its acetylated metabolite during treatment with olsalazine and mesalazine, 14 patients with inactive ulcerative colitis were randomly assigned to olsalazine (1 g twice daily) and the mesalazines, Asacol (800 + 400 + 800 mg daily), Pentasa (750 + 500 + 750 mg daily), and Salofalk (750 + 500 + 750 mg daily) in a crossover design trial so that all received each drug for seven days. Intraluminal colonic concentrations of 5-ASA were estimated after five days by the method of equilibrium in vivo dialysis of faeces. A predose serum sample and a 24 hour urine collection were obtained on day seven. The 5-ASA and acetyl-5-aminosalicylic acid (Ac-5-ASA) values were determined by high performance liquid chromatography. Olsalazine almost doubled the colonic concentrations (mean 23.7 (SEM) (1.9) mmol/l) of its therapeutically active ingredient (5-ASA) compared with equimolar doses of Pentasa (12.6 (2.2) mmol/l; p less than 0.0003) and Salofalk (15.0 (2.0) mmol/l; p less than 0.003). At the same time, olsalazine treatment was associated with lower serum concentrations and urinary excretions (p less than 0.05) of 5-ASA and Ac-5-ASA compared with the mesalazine preparations. The low systemic load of 5-ASA provided by olsalazine reduces the potential risk of nephrotoxicity during long term treatment.
Staerk Laursen
L
L
Department of Medical Gastroenterology, Odense University Hospital, Denmark.
Stokholm
M
M
Bukhave
K
K
Rask-Madsen
J
J
Lauritsen
K
K
D000328:Adult; D000368:Aged; D000636:Aminosalicylic Acids / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use* / Q000652:urine; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D019804:Mesalamine; D008875:Middle Aged
D000636:Aminosalicylic Acids; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D019804:Mesalamine; C028836:N-acetyl-5-aminosalicylic acid; C032587:olsalazine