Y. Watanabe et al., STUDIES OF DRUG-DELIVERY SYSTEMS FOR A THERAPEUTIC AGENT USED IN OSTEOPOROSIS - II - ENHANCED ABSORPTION OF ELCATONIN FROM NASAL-MUCOSA IN RABBITS, Biological & pharmaceutical bulletin, 21(11), 1998, pp. 1191-1194
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.