Gastroenterology

Gastroenterology

Volume 108, Issue 5, May 1995, Pages 1427-1433
Gastroenterology

Delivery and fate of oral mesalamine microgranules within the human small intestine

https://doi.org/10.1016/0016-5085(95)90691-6Get rights and content

Abstract

Background/Aims Oral use of mesalamine in inflammatory bowel disease requires slow-release preparations to prevent premature absorption and inactivation. Resulting luminal concentrations within the human small intestine are unknown. The aim of this study was to determine human intestinal delivery patterns of mesalamine from a microgranule preparation (Pentasa; Ferring Arzneimittel, Kiel, Germany) effective in Crohn's disease with small bowel involvement. Methods A multilumen tube for duodenal, jejunal, and ileal aspiration and marker perfusion was placed in 6 normal subjects. Levels of luminal, plasma, and urinary mesalamine and its main metabolite, acetyl mesalamine, were measured for 7 hours after ingestion of mesalamine (500 mg) with a labeled meal. Results Gastric emptying of mesalamine paralleled the meal, and its release occurred throughout the small intestine (cumulative, 20% of dose). For 4 hours, mean luminal mesalamine and acetyl mesalamine concentrations were 52 and 38 μg/mL (duodenum), 59 and 82 μg/mL (jejunum), and 64 and 104 μg/mL (ileum). Cumulative colonic delivery was 82% (7% dissolved, 75% in microgranules), and urinary excretion was 3.5%. Conclusions Although the major part of continuous-release mesalamine is delivered to the colon, large proportions are liberated and available at high concentrations within the small intestinal lumen, thus explaining its therapeutic efficacy in small intestinal Crohn's disease.

References (51)

  • MG Courtney et al.

    Randomised comparison of olsalazine and mesalazine in prevention of relapse in ulcerative colitis

    Lancet

    (1992)
  • JH Meyer et al.

    Human postprandial emptying of 1–3 mm spheres

    Gastroenterology

    (1988)
  • SB Hanauer

    Medical therapy of ulcerative colitis

    Lancet

    (1993)
  • AK Azad Khan et al.

    An experiment to determine the active therapeutic moiety of sulphasalazine

    Lancet

    (1977)
  • OH Nielsen et al.

    Kinetics of 5-aminosaticylic acid after jejunal instillation in man

    Br J Clin Pharmacol

    (1983)
  • B Myers et al.

    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

    (1987)
  • MCM Rijk et al.

    Disposition of 5-aminosalicylic acid by 5-aminosalicylic acid—delivering compounds

    Scand J Gastroenterol

    (1988)
  • ABR Thomson

    Coated oral 5-aminosalicylic acid versus placebo in maintaining remission of inactive Crohn's disease

    Aliment Pharmacol Ther

    (1990)
  • C Brignola et al.

    Placebo-controlled trial of oral mesalamine in relapse prevention of Crohn's disease

    Dig Dis Sci

    (1992)
  • U Klotz et al.

    A new slow-release form of 5-aminosalicylic acid for the oral treatment of inflammatory bowel disease

  • U Klotz et al.

    Pharmacokinetic properties of mesalazine (5-aminosalicylic acid)

  • SA Riley et al.

    Delayed-release mesalazine (5-aminosalicylic acid): coat dissolution and excretion in ileostoma subjects

    Br J Clin Pharmacol

    (1988)
  • LA Christensen et al.

    Topical and systemic availability of 5-aminosalicylate: comparisons of three controlled release preparations in man

    Aliment Pharmacol Ther

    (1990)
  • U Klotz

    Pharmacokinetic properties of 5-amino-salicylic acid (mesalazine)

  • JG Hardy et al.

    Gastrointestinal transit of an enteric-coated delayed-release 5-aminosalicylic acid tablet

    Aliment Pharmacol Therap

    (1987)
  • Cited by (77)

    • Mesalamine in the Initial Therapy of Ulcerative Colitis

      2020, Gastroenterology Clinics of North America
      Citation Excerpt :

      Pentasa contains mesalamine microgranules coated in a moisture-sensitive ethyl cellulose semipermeable membrane with release beginning in the duodenum and continuing throughout the GI tract.4 Therefore, 20% is released in the small bowel and the rest in the colonic epithelium; however, there may also be release in the stomach or proximal small bowel, depending on transit time.17 Balsalazide and olsalazine are prodrugs that require breakdown of enzyme-sensitive diazo bonds to produce active metabolites.

    • In vitro biorelevant models for evaluating modified release mesalamine products to forecast the effect of formulation and meal intake on drug release

      2015, European Journal of Pharmaceutics and Biopharmaceutics
      Citation Excerpt :

      The intake of a meal is known to alter the composition of the luminal gastrointestinal contents with regard to pH, buffer capacity, lipids, viscosity and osmolality [1–5]. In addition, the gastric emptying time of particles greater than approximately 2–7 mm, such as non-disintegrating monolithic dosage forms, can be greatly prolonged [4,6–10]. All of these factors can change the dissolution environment for solid oral dosage forms and may lead to an undesired change in the release rate.

    • Designing a biocompatible hydrogel for the delivery of mesalamine

      2015, International Journal of Pharmaceutics
      Citation Excerpt :

      Numerous in vitro studies found that the beneficial effects of 5-ASA are related to its anti-inflammatory and anti-oxidant properties within the inflamed gut (Clemett and Markham, 2000). One major drawback of 5-ASA is its fast absorbance in the upper gastrointestinal tract, leading to a relatively small amount reaching the colon (Layer et al., 1995). Additionally, this treatment has gastrointestinal, hematological and general side effects.

    • Aminosalicylates

      2011, Best Practice and Research: Clinical Gastroenterology
    View all citing articles on Scopus

    Supported by Deutsche Forschungsgemeinschaft, grant La 483/5-2, Robert Bosch Foundations (Stuttgart, Germany), and Ferring GmbH (Kiel, Germany).

    View full text