Degradation of Insulin and Calcitonin and Their Protection by Various Protease Inhibitors in Rat Caecal Contents: Implications in Peptide Delivery to the Colon

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  • Hideyuki Tozaki
    Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607,
  • Yasuharu Emi
    Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607,
  • Eri Horisaka
    Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607,
  • Takuya Fujita
    Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607,
  • Akira Yamamoto
    Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607,
  • Shozo Muranishi
    Department of Biopharmaceutics, Kyoto Pharmaceutical University , Misasagi, Yamashina-ku, Kyoto 607,

Bibliographic Information

Published
1997-02-01
Rights Information
  • https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model
DOI
  • 10.1111/j.2042-7158.1997.tb06773.x
Publisher
Oxford University Press (OUP)

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<jats:title>Abstract</jats:title><jats:p>The objective of this study was to examine the metabolism of insulin and calcitonin, and their protection by various protease inhibitors, in the large intestine.</jats:p><jats:p>Fresh caecal contents were prepared from non-fasted rats and the degradation of insulin and calcitonin was studied in a suspension of rat caecal contents, as a model of the content of the large intestine. Both insulin and calcitonin were metabolized in suspensions of rat caecal contents, but the degradation of calcitonin was much faster than that of insulin. The degradation of insulin was fastest at pH 6.8. Protease inhibitors such as camostat and aprotinin inhibited the degradation of insulin and calcitonin in rat caecal contents, which was consistent with the high chymotrypsin activity of these contents.</jats:p><jats:p>These findings suggest that care should be taken when administering peptide drugs to the large intestine for colon-specific drug delivery because they can be degraded in rat caecal contents. Protease inhibitors might be useful for increasing the stability of these peptides in the large intestine, thereby improving their large-intestinal absorption to the systemic circulation.</jats:p>

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