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  • Title: Use of protease inhibitors to improve calcitonin absorption from the small and large intestine in rats.
    Author: Tozaki H, Odoriba T, Iseki T, Taniguchi T, Fujita T, Murakami M, Muranishi S, Yamamoto A.
    Journal: J Pharm Pharmacol; 1998 Aug; 50(8):913-20. PubMed ID: 9751457.
    Abstract:
    The objective of this study was to examine the effects of protease inhibitors on the absorption of calcitonin from different regions of the intestine in rats. The absorption experiments were investigated by in-situ use of closed intestinal loops in rats and stability of calcitonin was examined in mucosal homogenates and intestinal fluids. The intestinal absorption of calcitonin was evaluated by measurement of its hypocalcaemic effect. No substantial hypocalcaemic response was observed when calcitonin was administered into the jejunum or colon. A slight hypocalcaemic effect was observed after administration of calcitonin into the ileum. Of the co-administered protease inhibitors, bacitracin (20mM) strongly promoted calcitonin absorption from the jejunum, ileum and colon. A significant hypocalcaemic effect was also obtained after intestinal administration of calcitonin with soybean trypsin inhibitor (10mgmL(-1)), camostat mesylate (20mM) or aprotinin (2mgmL(-1)). In the stability experiment, bacitracin reduced the degradation of calcitonin in the different intestinal homogenates. Soybean trypsin inhibitor significantly reduced the degradation of calcitonin in the fluids of the small intestine. We also examined the different endopeptidases in gut luminal fluids and the different exopeptidases in gut mucosal homogenates of rats. The ranking order for the total endopeptidase activity of the intestinal fluids was jejunum > ileum > colon. That for total exopeptidase activity of the intestinal mucosa was jejunum > ileum > colon. These results suggest that endo- and exopeptidases might be responsible for the hydrolysis of calcitonin and that protease inhibitors might usefully improve absorption of calcitonin to the systemic circulation from the large intestine.
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