Studies of drug delivery systems for a therapeutic agent used in osteoporosis. II. Enhanced absorption of elcatonin from nasal mucosa in rabbits.

Abstract

In this study, the effects of a protease inhibitor, endocytosis inhibitors and an absorption-enhancing agent on the absorption of ((Asu1,7)-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 efficiently absorbed from the nasal mucous membrane and effectively decreased serum calcium (Ca) concentrations. The increase in the area under the percent decrease in serum Ca concentration (deltaCa%)-time curve (deltaCa%-AUC) value, assumed to be an index of the pharmacodynamics (hypocalcemic effect) of ECT, depended on the dose of ECT administered intranasally. When nafamostat mesilate, a protease inhibitor, was coadministered with ECT, the deltaCa%-AUC markedly increased. It is presumed that the influence (enzymatic barrier function) of protease on the nasal absorption of ECT is significant. However, no significant difference in the deltaCa%-AUC value was observed when an endocytosis inhibitor (cytochalasin B or monensin) was coadministered with ECT. ECT administration in combination with sodium decanoate, the sodium salt of a medium-chain fatty acid, effectively increased the deltaCa%-AUC value due to the enhancing effect of sodium decanoate on the nasal absorption of ECT. We conclude that the nasal application offers a promising approach for the administration of pharmaceutical preparations containing ECT with additives such as nafamostat mesilate and sodium decanoate.