| 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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MedLine Citation:
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PMID: 9055189 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. 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. 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. |
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Authors:
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H Tozaki; Y Emi; E Horisaka; T Fujita; A Yamamoto; S Muranishi |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: The Journal of pharmacy and pharmacology Volume: 49 ISSN: 0022-3573 ISO Abbreviation: J. Pharm. Pharmacol. Publication Date: 1997 Feb |
Date Detail:
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Created Date: 1997-05-22 Completed Date: 1997-05-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376363 Medline TA: J Pharm Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 164-8 Citation Subset: IM |
Affiliation:
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Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aprotinin / pharmacology Calcitonin / metabolism* Cecum / drug effects, metabolism* Endopeptidases / metabolism Gabexate* / analogs & derivatives* Guanidines / pharmacology Hydrogen-Ion Concentration Insulin / metabolism* Male Protease Inhibitors / pharmacology* Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/Guanidines; 0/Protease Inhibitors; 11061-68-0/Insulin; 39492-01-8/Gabexate; 59721-28-7/FOY 305; 9007-12-9/Calcitonin; 9087-70-1/Aprotinin; EC 3.4.-/Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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