Absorption enhancing effect of labrasol on the intestinal absorption of insulin in rats.
The oral absorption enhancing effect of Labrasol has been studied in rats using insulin as a model peptide/protein drug. Insulin solution was prepared by dissolving insulin in pH 7.4 buffer followed by the addition of Labrasol. The insulin concentration was 50.0 IU/ml. The test insulin/Labrasol solution was administered to the jejunum, ileum and ascending colon of rats at 10.0 IU/kg. After administration, blood samples were collected for 5 h and serum glucose levels and insulin levels were measured. In another group of rats, insulin solution was injected intravenously at 1.0 IU/kg, and both serum glucose and insulin levels were measured. The pharmacological availability of insulin from Labrasol solution was found to be 3.9, 8.9 and 9.1% following jejunal, ileal and colonic administrations, respectively, by comparing the serum glucose level vs. time profiles obtained after intestinal and i.v. administrations. By comparing the serum insulin levels vs. time profiles, the bioavailability of insulin was found to be 0.25 and 0.20% for intra-ileum and colonic administrations, respectively. The hypoglycemic effect of insulin after intra-ileum administration showed a dose-dependency in the insulin dose range from 10.0 to 1.0 IU/kg. These results suggest the absorption enhancing effect of Labrasol on the intestinal absorption of insulin in rats.
Eaimtrakarn
Sudarat
S
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Japan.
Rama Prasad
Y V
YV
Ohno
Tomoya
T
Konishi
Takahiro
T
Yoshikawa
Yukako
Y
Shibata
Nobuhito
N
Takada
Kanji
K
D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004655:Emulsions / Q000494:pharmacology*; D005989:Glycerides; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007082:Ileum / Q000378:metabolism; D007275:Injections, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D007583:Jejunum / Q000378:metabolism; D008297:Male; D009930:Organic Chemicals; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D004337:Drug Carriers; D004655:Emulsions; D005989:Glycerides; D007004:Hypoglycemic Agents; D007328:Insulin; D009930:Organic Chemicals; C440220:Labrasol