title: Effects of absorption promoters on insulin absorption through colon-targeted delivery.
abstract: The aim of this study were to investigate the effect of sodium glycocholate (GC-Na) as an absorption promoter and the effects of the co-administration of GC-Na and various absorption promoters on orally administered insulin absorption utilizing a colon-targeted delivery system. The system containing insulin and GC-Na (CDS) was administered to dogs, and plasma glucose and insulin levels were then measured at 24h after administration. For CDS, the C(max) in plasma glucose level was significantly higher than a reference formulation without GC-Na. The pharmacological availability for CDS was not significantly higher than the reference formulation. In contrast, CDS with poly(ethylene oxide) as a gelling agent (CDSP) showed prolonged hypoglycemia effects. The pharmacological availability was 5.5% and significantly different from the reference formulation. The absolute bioavailability for CDS was 0.25%, and for CDSP it was 0.42%. Consequently, the results of this study demonstrated that colon-specific delivery of insulin with GC-Na was more effective in increasing hypoglycemic effects after oral administration, and the combination of GC-Na and poly(ethylene oxide) tended to prolong the colonic absorption of insulin and might be more effective for improvement of orally administered insulin absorption utilizing the colon-targeted delivery system.
authors.affiliation: Pharmaceutical Technology Administration, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan. masataka.katsuma@jp.astellas.com
authors.forename: Masataka
authors.initials: M
authors.lastname: Katsuma
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Watanabe
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kawai
authors.forename: Shigeo
authors.initials: S
authors.lastname: Takemura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sako
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations; D004285:Dogs; D016503:Drug Delivery Systems; D006000:Glycocholic Acid / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D007328:Insulin; D011092:Polyethylene Glycols; D006000:Glycocholic Acid