STUDIES OF DRUG-DELIVERY SYSTEMS FOR A THERAPEUTIC AGENT USED IN OSTEOPOROSIS - II - ENHANCED ABSORPTION OF ELCATONIN FROM NASAL-MUCOSA IN RABBITS

In this study, the effects of a protease inhibitor, endocytosis inhibi tors and an absorption-enhancing agent on the absorption of ((Asu(1,7) )-eel calcitonin, ECT) from the nasal mucous membrane in rabbits were examined, and the results were compared with those obtained following the rectal absorption of ECT reported in our previous paper. ECT was e fficiently absorbed from the nasal mucous membrane and effectively dec reased serum calcium (Ca) concentrations. The increase in the area und er the percent decrease in serum Ca concentration (Delta Ca%)-time cur ve (Delta Ca%-AUC) value, assumed to be an index of the pharmacodynami cs (hypocalcemic effect) of ECT, depended on the dose of ECT administe red intranasally. When nafamostat mesilate, a protease inhibitor, was coadministered with ECT, the Delta Ca%-AUC markedly increased. It is p resumed that the influence (enzymatic barrier function) of protease an the nasal absorption of ECT is significant. However, no significant d ifference in the Delta Ca%-AUC value was observed when an endocytosis inhibitor (cytochalasin B or monensin) was coadministered with ECT. EC T administration in combination with sodium decanoate, the sodium salt of a medium-chain fatty acid, effectively increased the Delta Ca%-AUC value due to the enhancing effect of sodium decanoate on the nasal ab sorption of ECT. We conclude that the nasal application offers a promi sing approach for the administration of pharmaceutical preparations co ntaining ECT with additives such as nafamostat mesilate and sodium dec anoate.