PHARMACEUTICAL EVALUATION OF HOLLOW TYPE SUPPOSITORIES, PART XXII - STUDIES OF DRUG-DELIVERY SYSTEMS FOR A THERAPEUTIC AGENT USED IN OSTEOPOROSIS - I - PHARMACODYNAMICS (HYPOCALCEMIC EFFECT) OF ELCATONIN IN RABBITS FOLLOWING RECTAL ADMINISTRATION OF HOLLOW-TYPE SUPPOSITORIES CONTAINING ELCATONIN

In this study, we developed a new hollow-type suppository containing e lcatonin ((Asu(1,7))-eel calcitonin, ECT), a synthetic derivative of e el calcitonin, which produces hypocalcemia, as a pharmaceutical prepar ation for self administration, to be used instead of parenteral inject ions for patients,vith osteoporosis. The absorption of ECT from the re ctal mucous membrane was evaluated by observation of the decrease in s erum calcium (Ca) concentrations following rectal administration in ra bbits. ECT was efficiently absorbed from the rectum and effectively de creased serum Ca concentrations. The data of the area under the percen t decrease in serum Ca concentration (Delta Ca%)-time curve (Delta Ca% -AUC), assumed to be an index of the pharmacodynamics (pharmacological effect) of ECT, indicated that similar hypocalcemic effects were obta ined following rectal and intravenous administrations of ECT. In regar d to the effect of coadministration of other compounds on rectal absor ption of ECT, no significant difference in the Delta Ca%-AUC between r ectal ECT administration with or without nafamostat mesilate (a protea se inhibitor) was observed. However, the coadministration of ECT with cytochalasin B or monensin (endocytosis inhibitors) significantly decr eased the Delta Ca%-AUC, indicating that rectal ECT absorption is prob ably inhibited by endocytosis inhibitors. On the other hand, it was fo und that sodium decanoate, a medium-chain fatty acid (sodium salt), si gnificantly enhanced the rectal absorption of ECT. We conclude that th is ECT hollow-type suppository offers promise as a new method for the administration of ECT.