title: Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration.
abstract: BACKGROUND
  6-Mercaptopurine and its prodrug azathioprine are effective medications for refractory inflammatory bowel disease. However, use of these drugs has been limited by concerns about their toxicity. Colonic delivery of azathioprine may reduce its systemic bioavailability and limit toxicity.
  
  
  OBJECTIVE
  To determine the bioavailability of 6-mercaptopurine after administration of azathioprine via three colonic delivery formulations.
  
  
  METHODS
  Twenty four healthy human subjects each received 50 mg of azathioprine by one of four delivery formulations (each n = 6): oral; delayed release oral; hydrophobic rectal foam; and hydrophilic rectal foam. All subjects also received a 50 mg dose of intravenous azathioprine during a separate study period. Plasma concentrations of 6-mercaptopurine were determined by high pressure liquid chromatography.
  
  
  RESULTS
  The bioavailabilities of 6-mercaptopurine after colonic azathioprine administration via delayed release oral, hydrophobic rectal foam, and hydrophilic rectal foam (7%, 5%, 1%; respectively) were significantly lower than the bioavailability of 6-mercaptopurine after oral azathioprine administration (47%) by Wilcoxon rank sum pairwise comparison.
  
  
  CONCLUSIONS
  Azathioprine delivered to the colon by delayed release oral and rectal foam formulations considerably reduced systemic 6-mercaptopurine bioavailability. The therapeutic potential of these colonic delivery methods, which can potentially limit toxicity by local delivery of high doses of azathioprine, should be investigated in patients with inflammatory bowel disease.
authors.affiliation: Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Van Os
authors.forename: B J
authors.initials: BJ
authors.lastname: Zins
authors.forename: W J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: D C
authors.initials: DC
authors.lastname: Mays
authors.forename: W J
authors.initials: WJ
authors.lastname: Tremaine
authors.forename: D W
authors.initials: DW
authors.lastname: Mahoney
authors.forename: A R
authors.initials: AR
authors.lastname: Zinsmeister
authors.forename: J J
authors.initials: JJ
authors.lastname: Lipsky
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D015122:Mercaptopurine / Q000097:blood*; D008875:Middle Aged
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine