Abstract
Effects of protease inhibitors and absorption enhancers on the absorption of salmon calcitonin (sCT) were evaluated after intratracheal coadministration to rats using the plasma Ca level as an index. Remarkable absorption enhancement could be attained with unsaturated fatty acids such as oleic acid and polyoxyethylene oleyl ether (absorption enhancers) and with chymostatin, bacitracin, potato carboxypeptidase inhibitor and phosphoramidon (protease inhibitors). sCT degrading enzymes had four times higher activity per total protein in membrane fraction of lung homogenates than the activity in cytosol fraction. These enzymes are thought to be serine proteases and metalloenzymes from the in vitro action profile of protease inhibitors. A good correlation between the in vitro activity of protease inhibitors and the in vivo enhancing effect on sCT activity suggested that membrane enzymes are responsible for the inactivation of sCT. Metabolic degradation and low permeability of sCT may be possible barriers to the absorption of sCT.
Published Version
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