Effects of proteolytic enzyme inhibitors as absorption enhancers on the transdermal iontophoretic delivery of calcitonin in rats.
The effects of proteolytic enzyme inhibitors, aprotinin, soybean trypsin inhibitor and camostat mesilate as absorption enhancers on the transdermal iontophoretic delivery of salmon calcitonin (SCT) have been examined in rats. The dermal absorption of SCT was evaluated with hypocalcaemic effect. Application of SCT (12.5 int. units/rat) onto abdominal skin did not produce any hypocalcaemic effect. This produced a small hypocalcaemic effect with cationic iontophoresis (drug phase, anode; reference phase, cathode; high frequency pulses of 1 V at 10 kHz, 2h). Furthermore, camostat mesilate (1 mM) and aprotinin (10(6) int. units mL-1) enhanced the hypocalcaemic effects on the application of SCT with iontophoresis. These hypocalcaemic effects were highest with the pH 4.0 preparation compared with those of the pH 5.5, pH 7.0 and pH 8.0 preparations. However, soybean trypsin inhibitor did not change the hypocalcaemic effects. This was because the soybean trypsin inhibitor is a relatively high molecular weight peptide (mol. wt 8000) and an anion at used pH, and therefore was not absorbed through rat skins with cation iontophoresis.
Department of Pharmaceutics, Osaka University of Pharmaceutical Sciences, Japan.
K
K
Morimoto
Y
Y
Iwakura
E
E
Nakatani
M
M
Miyazaki
H
H
Tojima
D000042:Absorption; D000279:Administration, Cutaneous; D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006996:Hypocalcemia / Q000097:blood / Q000139:chemically induced; D007478:Iontophoresis; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011480:Protease Inhibitors; C028815:salmon calcitonin; D002116:Calcitonin