Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration

E. C. Van Os, B. J. Zins, W. J. Sandborn, D. C. Mays, W. J. Tremaine, D. W. Mahoney, A. R. Zinsmeister, J. J. Lipsky

Research output: Contribution to journalArticle

79 Citations (Scopus)

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. Aim - 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.

Original languageEnglish (US)
Pages (from-to)63-68
Number of pages6
JournalGut
Volume39
Issue number1
StatePublished - 1996

Fingerprint

Rectal Administration
Azathioprine
6-Mercaptopurine
Pharmacokinetics
Biological Availability
Inflammatory Bowel Diseases
Prodrugs
Oral Administration
Healthy Volunteers
Colon
High Pressure Liquid Chromatography

Keywords

  • 6- mercaptopurine
  • azathioprine
  • Crohn's disease
  • inflammatory bowel disease
  • pharmacokinetics
  • ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Van Os, E. C., Zins, B. J., Sandborn, W. J., Mays, D. C., Tremaine, W. J., Mahoney, D. W., ... Lipsky, J. J. (1996). Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration. Gut, 39(1), 63-68.

Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration. / Van Os, E. C.; Zins, B. J.; Sandborn, W. J.; Mays, D. C.; Tremaine, W. J.; Mahoney, D. W.; Zinsmeister, A. R.; Lipsky, J. J.

In: Gut, Vol. 39, No. 1, 1996, p. 63-68.

Research output: Contribution to journalArticle

Van Os, EC, Zins, BJ, Sandborn, WJ, Mays, DC, Tremaine, WJ, Mahoney, DW, Zinsmeister, AR & Lipsky, JJ 1996, 'Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration', Gut, vol. 39, no. 1, pp. 63-68.
Van Os EC, Zins BJ, Sandborn WJ, Mays DC, Tremaine WJ, Mahoney DW et al. Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration. Gut. 1996;39(1):63-68.
Van Os, E. C. ; Zins, B. J. ; Sandborn, W. J. ; Mays, D. C. ; Tremaine, W. J. ; Mahoney, D. W. ; Zinsmeister, A. R. ; Lipsky, J. J. / Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration. In: Gut. 1996 ; Vol. 39, No. 1. pp. 63-68.
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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. Aim - 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.",
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T1 - Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration

AU - Van Os, E. C.

AU - Zins, B. J.

AU - Sandborn, W. J.

AU - Mays, D. C.

AU - Tremaine, W. J.

AU - Mahoney, D. W.

AU - Zinsmeister, A. R.

AU - Lipsky, J. J.

PY - 1996

Y1 - 1996

N2 - 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. Aim - 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.

AB - 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. Aim - 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.

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KW - azathioprine

KW - Crohn's disease

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