Improvement of the Pulmonary Absorption of (Asu1,7)-Eel Calcitonin by Various Protease Inhibitors in Rats |
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Authors: | Morita Takahiro Yamamoto Akira Takakura Yoshinobu Hashida Mitsuru Sezaki Hitoshi |
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Affiliation: | (1) Department of Basic Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606, Japan;(2) Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607, Japan;(3) Faculty of Pharmaceutical Sciences, Setsunan University, Nagao-toge-cho 45-1, Hirakata, Osaka, 573-01, Japan |
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Abstract: | The effects of protease inhibitors, Na-glycocholate, bacitracin, bestatin, nafamostat mesilate and soybean trypsin inhibitor (STI) on the pulmonary absorption of (Asu1,7)-eel calcitonin (ECT, molecular weight 3363) were investigated in rats. The pulmonary absorption of ECT was estimated by measuring its hypocalcemic effect. When ECT alone was administered into the lung, the pharmacological availability of ECT was 2.7%. Co-administration with STI or bestatin did not change the pharmacological effect of ECT. However, Na-glycocholate, bacitracin and nafamostat mesilate caused a significant hypocalcemic effect following the pulmonary absorption of ECT and a maximal effect was noted in the presence of 20 mM bacitracin, approaching the effect after intravenous administration of ECT. Bacitracin and Na-glycocholate reduced the degradation of 111In-ECT in rat lung homogenate. Therefore, protease inhibitors effectively improved the pulmonary absorption of ECT. |
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Keywords: | pulmonary absorption protease inhibitor calcitonin Na-glycocholate bacitracin pharmacological availability |
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