Promotion of nasal absorption of insulin by glycyrrhetinic acid derivatives. I.
Nasal absorption of insulin in rats was enhanced by addition of sodium glycyrrhetinate (GA Na), dipotassium glycyrrhizinate (GZ K2), and carbenoxolone (glycyrrhetinic acid hydrogen succinate) disodium salt (GAHS Na2). The latter agent was the most effective. On addition of 1% GAHS Na2, plasma immunoreactive insulin levels in rats showed a maximum level of 0.75 mU/ml at 15 min and plasma glucose levels were decreased to about 25 mg/dl after nasal administration of 10 U/kg insulin. In a comparison of the absorption rates of insulin by nasal and intravenous (i.v.) routes in rats, nasal absorptions of 10 U/kg insulin in the presence of 1% GAHS Na2, 0.5% GA Na and 1% GZ K2 were 26.5%, 13.2% and 14.5% of that in the case of a 5 U/kg i.v. dose, respectively. Hemolytic activies of GAHS Na2, GA Na and GZ K2 were milder than those of Na caprate and Na laurate, and nasal leucine aminopeptidase activity was more strongly inhibited by GAHS Na2 than by medium chain fatty acid salts, sodium glycocholate, GA Na or GZ K2. Therefore, it is suggested that GAHS Na2 is a very useful promoter which dose not irritate the nasal mucosal membrane or degrade insulin.
Mishima
M
M
Department of Pharmaceutical Services, Kumamoto University Hospital, Japan.
Okada
S
S
Wakita
Y
Y
Nakano
M
M
D000042:Absorption; D000281:Administration, Intranasal; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002229:Carbenoxolone / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D007328:Insulin / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics*; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D007931:Leucyl Aminopeptidase; D002229:Carbenoxolone; D006034:Glycyrrhetinic Acid