title: Antihyperglycemic effect of insulin from self-dissolving micropiles in dogs.
abstract: As a percutaneous delivery device, self-dissolving micropiles (SDMPs) composed of chondroitin sulfate and insulin were prepared under room temperature from highly concentrated solution, glue. The mean weight of SDMP was 1.03+/-0.04 mg. One insulin SDMP was percutaneously administered to the shaved abdominal skin of four beagle dogs at insulin dose level of 1.0 and 2.0 IU/dog. After administration, blood samples were collected for 6 h and plasma glucose levels were measured. The time when minimum plasma glucose level appeared, T(min), was 1.38+/-0.2 h for 1.0 IU study and 1.38+/-0.1 h for 2.0 IU study and clear dose-dependent hypoglycemic effect of insulin was observed in the dose range. By comparing the area above the plasma glucose level vs. time curve (AAC) between insulin SDMP and subcutaneous (s.c.) injection solution, the relative pharmacological availabilities were 99% (1.0 IU) and 90% (2.0 IU), respectively. To ascertain the usefulness of insulin SDMP, oral glucose tolerance test (OGTT) was performed. When dogs were treated with insulin SDMPs, 2.0 IU, followed by an OGTT 30 min, glycemia did not appear for 5 h. On the other hand, when OGTT was performed at 1 h after insulin SDMP administration, hypoglycemia appeared as in the case of s.c. injection of insulin solution, 2.0 IU. Insulin SDMP improved the oral glucose challenge for 3 h, with a maximum effect at 30 min before the administration of glucose. Those results suggest the usefulness of a SDMP for the percutaneous delivery of peptide/protein drugs like insulin.
authors.affiliation: Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan. yukako@mb.kyoto-phu.ac.jp
authors.forename: Yukako
authors.initials: Y
authors.lastname: Ito
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saeki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sugioka
authors.forename: Kanji
authors.initials: K
authors.lastname: Takada
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000737:chemistry; D004285:Dogs; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D008863:Microspheres; D019999:Pharmaceutical Solutions
chemical_list: D001786:Blood Glucose; D005079:Excipients; D007004:Hypoglycemic Agents; D007328:Insulin; D019999:Pharmaceutical Solutions; D002809:Chondroitin Sulfates