Percutaneous absorption of elcatonin and hypocalcemic effect in rat.
The percutaneous absorption of elcatonin (EC), a hypocalcemic peptide, was investigated. A transdermal dosage form of EC was produced using a gel base, absorption enhancer and protease inhibitor, and applied to rats for 24 h. The combination of bile salt such as taurocholate and glycocholate, and n-octyl-beta-D-glucoside or n-octyl-beta-D-thioglucoside (OTG) exerted the potent enhancing effect on the absorption of EC, and a potent hypocalcemic effect was shown for 24 h or longer. The least level of plasma calcium was obtained 6 h or longer after application, suggesting the relatively rapid absorption of EC. The apparent bioavailability of EC in system 5 was 4.6%, this value being noteworthy in the percutaneous absorption of peptides. When the enhancing effect of taurocholate and OTG was separately measured, both agents acted additively on the absorption of EC. An EC ointment maintained the hypocalcemin effect after storage for 15 d at 40 degrees C. The transdermal dosage form has the potential to be an efficient drug delivery system for Paget's disease and osteoporosis.
Ogiso
T
T
Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan.
Iwaki
M
M
Yoneda
I
I
Horinouchi
M
M
Yamashita
K
K
D000818:Animals; D002116:Calcitonin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D003864:Depression, Chemical; D008297:Male; D051381:Rats; D012869:Skin Absorption
D002116:Calcitonin; D002118:Calcium; C012755:elcatonin