Abstract
The bioavailability of a controlled release 5-aminosalicylic acid preparation (Pentasa) was investigated in nine healthy children after a medication period of six days (1000 mg/day) and compared with sulfasalazine (Salazopyrin) (2000 mg/day). The local bioavailability in the distal gut lumen, reflected by the 5-aminosalicylic acid concentration in the fecal water, showed comparable values after Pentasa (4.44 mmol/liter) and Salazopyrin (6.25 mmol/liter). The concentration ofN-acetyl-5-ASA was significantly higher after Pentasa, reflecting the more proximal release of 5-aminosalicylic acid compared with Salazopyrin. No relation was found between the 5-aminosalicylic acid fecal water concentration and the 5-aminosalicylic acid dose per kilogram of body weight. The urinary excretion of 5-aminosalicylic acid andN-acetyl-5-aminosalicylic acid was higher after Pentasa than after Salazopyrin (32% vs 25%). Dose interval plasma concentration curves showed low values after both preparations. Based on the concept that the fecal water concentration is decisive for the efficacy of 5-aminosalicylic acid in distal inflammatory bowel disease, Pentasa treatment offers a relevant alternative in cases of Salazopyrin intolerance or allergy in children. The higher systemic bioavailability from Pentasa warrants monitoring of the renal function.
Similar content being viewed by others
References
Dew MJ, Hughes P, Harries AD, Williams G, Evans BK, Rhodes J: Maintenance of remission in ulcerative colitis with oral preparation of 5-aminosalicylic acid. Br Med J 285:1012, 1982
Rutgeers P: Comparative efficacy of coated, oral 5-aminosalicylic acid (Claversal®) and sulphasalazine for maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 3:183–191, 1989
Mulder CJJ, Tytgat GNJ, Weterman IT, Dekker W, Blok P, Schrijver M, v d Heide H: Double-blind comparison of slow-release 5-aminosalicylic acid and sulfasalazine in remission maintenance in ulcerative colitis. Gastroenterology 95:1449–1453, 1989
Riley SA, Mani V, Goodman MJ, Herd ME, Dutt S: Comparison of delayed release 5-aminosalicylic acid (mesalazine) and sulphasalazine in treatment of mild to moderate ulcerative colitis relapse. Gut 29:669–674, 1988
Hanauer S, Schwartz J, Roufail W, Robinson M, Cello J, Safdi M, Guernsey B, Beshears L: Dose-ranging study of oral mesalazine capsule (Pentasa®) for active ulcerative colitis. Gastroenterology 96:195, 1989 (abstract)
Rachmilewitz D: Mesalazine (5-ASA) is as effective as sulfasalazine (SZ) in the treatment of active ulcerative colitis. Gastroenterology 94:362, 1988 (abstract)
Dew MJ, Ryder REJ, Evans N, Evans BK, Rhodes J: Colonic release of 5-aminosalicylic acid from an oral preparation in active ulcerative colitis. Br J Clin Pharmacol 16:185–187, 1983
Klotz U, Maier KE, Fischer C, Bauer KH: A new slow-release from of 5-aminosalicylic acid for the treatment of inflammatory bowel disease. Arzneim Forsch Drug Res 35:636–639, 1985
Rijk CMC, van Schaik A, van Tongeren JHM: Disposition of 5-aminosalicylic acid by 5-aminosalicylic acid-delivering compounds. Scand J Gastroenterol 23:107–112, 1988
Christensen LA, Fallingborg J, Abildgaard K, Jacobsen BA, Sanchez G, Hansen SH, Bondesen S, Hvidberg EF, Nørby Rasmussen SN: Topical and systemic availability of 5-aminosalicylate: Comparisons of three controlled release preparations in man. Aliment Pharmacol Ther 4:523–533, 1990
Tolia V, Massoud N, Klotz U: Oral 5-aminosalicylic acid in children with colonic chronic inflammatory bowel disease. Clinical and pharmacokinetic experience. J Pediatr Gastroenterol Nutr 8:331–338, 1989
Rasmussen SN, Bondesen S, Hvidberg EF, Hansen SH, Binder V, Halskov S, Flachs H: 5-Aminosalicylic acid in a slow release preparation: Bioavailability, plasma level, and excretion in humans. Gastroenterology 83:1062–1070, 1982
Christensen LA, Slot O, Sanchez G, Boserup J, Rasmussen SN, Bondesen S, Hansen SH, Hvidberg EF: Release of 5-aminosalicylic acid from Pentasa during normal and accelerated intestinal transit time. Br J Clin Pharmacol 23:365–369, 1987
Hansen SH: A simple and rapid method for simultaneous determination of the eight main metabolites and conjugates of sulfasalazine in plasma, urine and faeces using dynamically modified silica. J Chromatogr 491:175–185, 1989
Bondesen S, Nielsen OH, Schou JB, Jensen PH, Lassen LB, Binder V, Krasilnikoff PA, Danø P, Hansen SH, Rasmussen SN, Hvidberg EF: Steady-state kinetics of 5-aminosalicylic acid and sulfapyridine during sulfasalazine prophylaxis in ulcerative colitis. Scand J Gastroenterol 21:693–700, 1986
Azad Khan AK, Piris J, Truelove SC: An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet 2:892–895, 1977
van Hees PAM, Bakker JH, van Tongeren JHM: Effect of sulphapyridine, 5-aminosalicylic acid, and placebo in patients with idiopathic proctitis: A study to determine the active therapeutic moiety of sulphasalazine. Gut 21:632–635, 1980
Myers B, Evans DNW, Rhodes JBK, Hughes BR, Lee MG, Richens A, Richards D: Metabolism and urinary excretion of 5-aminosalicylic acid in healthy volunteers when given intravenously or released for absorption at different sites in the gastrointestinal tract. Gut 28:196–200, 1987
Binder V, Halskov S, Hvidberg EF: A controlled study of 5-acet-aminosalicylic acid as enema in ulcerative colitis. Scand J Gastroenterol 16:1122, 1981
Willoughby CP, Piris J, Truelove SC: The effect of topicalN-acetyl-5-aminosalicylic acid in ulcerative colitis. Scand J Gastroenterol 15:715–719, 1980
Nielsen OH, Bondesen S: Kinetics of 5-Aminosalicylic acid after jejunal instillation in man. Br J Clin Pharmacol 16:738–740, 1983
Novis BH, Kotzets Z, Chen P, Bernheim J: Nephrotic syndrome after treatment with 5-aminosalicylic acid. Br Med J 296:1442, 1988
von Myhlendahl KE: Nephritis during 5-aminosalicylic acid. Dtsch Med Wochenschr 114:236, 1989
Calder IC, Funder CC, Green CR, Ham KN, Tange JD: Nephrotoxic lesions from 5-aminosalicylic acid. Br Med J 1:152–154, 1972
van Hees PAM: Clinical and pharmacological aspects of sulfasalazine. Thesis. 1979
Rao SSC, Read NW, Brown C, Bruce C, Holdsworth CD: Studies on the mechanism of bowel disturbance in ulcerative colitis. Gastroenterology 93:934–940, 1987
Allison MC, Dick R, Pounder RE: A controlled study of faecal distribution in ulcerative colitis and proctitis. Scand J Gastroenterol 22:1277–1280, 1987
Rijk MCM, van Hogezand RA, van Schaik A, van Tongeren JHM: Disposition of 5-aminosalicylic acid-delivering drugs during accelerated inteatinal transit in healthy volunteers. Scand J Gastroenterol 24:1179–1185, 1989
Author information
Authors and Affiliations
Additional information
The study was supported by Alfred Benzon Foundation. Pentasa tablets were kindly supplied by Ferring A/S, Denmark and Salazopyrin by Pharmacia Ltd, Sweden.
Rights and permissions
About this article
Cite this article
Christensen, L.A., Fallingborg, J., Jacobsen, B.A. et al. Bioavailability of 5-aminosalicylic acid from slow release 5-aminosalicylic acid drug and sulfasalazine in normal children. Digest Dis Sci 38, 1831–1836 (1993). https://doi.org/10.1007/BF01296106
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01296106