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 elcatonin ((Asu1,7)-eel calcitonin, ECT), a synthetic derivative of eel calcitonin, which produces hypocalcemia, as a pharmaceutical preparation for self administration, to be used instead of parenteral injections for patients with osteoporosis. The absorption of ECT from the rectal mucous membrane was evaluated by observation of the decrease in serum calcium (Ca) concentrations following rectal administration in rabbits. ECT was efficiently absorbed from the rectum and effectively decreased serum Ca concentrations. The data of the area under the percent decrease in serum Ca concentration (deltaCa%)-time curve (deltaCa%-AUC), assumed to be an index of the pharmacodynamics (pharmacological effect) of ECT, indicated that similar hypocalcemic effects were obtained following rectal and intravenous administrations of ECT. In regard to the effect of coadministration of other compounds on rectal absorption of ECT, no significant difference in the deltaCa%-AUC between rectal ECT administration with or without nafamostat mesilate (a protease inhibitor) was observed. However, the coadministration of ECT with cytochalasin B or monensin (endocytosis inhibitors) significantly decreased the deltaCa%-AUC, indicating that rectal ECT absorption is probably inhibited by endocytosis inhibitors. On the other hand, it was found that sodium decanoate, a medium-chain fatty acid (sodium salt), significantly enhanced the rectal absorption of ECT. We conclude that this ECT hollow-type suppository offers promise as a new method for the administration of ECT.
Watanabe
Y
Y
Department of Pharmaceutics, Showa College of Pharmaceutical Sciences, Machida, Tokyo, Japan.
Mizufune
Y
Y
Kubomura
A
A
Kiriyama
M
M
Utoguchi
N
N
Matsumoto
M
M
D000042:Absorption; D000285:Administration, Rectal; D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000378:metabolism; D016503:Drug Delivery Systems; D006996:Hypocalcemia / Q000139:chemically induced; D007275:Injections, Intravenous; D008297:Male; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D011817:Rabbits; D013488:Suppositories
D013488:Suppositories; D002116:Calcitonin; D002118:Calcium; C012755:elcatonin