Nasal absorption of mixtures of fast-acting and long-acting insulins.
Mixtures of fast-acting and long-acting insulins were administered nasally to anesthetized, hyperglycemic rats in the presence and absence of tetradecyl-beta-d-maltoside (TDM). The fast-acting analogs, aspart insulin, lispro insulin and glulisine insulin, were all rapidly absorbed from the nose when applied individually with 0.125% TDM (T(max)=15min). One long-acting insulin analog, glargine insulin, was also absorbed from the nose when applied individually in the presence of 0.125% TDM (T(max)=60min). The other long-acting insulin analog, detemir insulin, was not soluble when formulated with 0.125% TDM. A series of mixtures (1:1) of the three rapid-acting insulins and long-acting glargine insulin were formulated with 0.125% TDM and applied nasally. The pharmacokinetic and pharmacodynamic profiles of the insulin mixtures reflected the additive contributions of both the rapid-acting and the long-acting insulins. These results support the possibility of formulating certain insulin mixtures in tandem to provide nasal insulin products that match the needs of patients with diabetes mellitus better than those currently available.
Pillion
Dennis J
DJ
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 1530 3rd Ave S, Birmingham, AL 35294-0019, United States. dpillion@uab.edu
Fyrberg
Michael D
MD
Meezan
Elias
E
D000281:Administration, Intranasal; D000818:Animals; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D005079:Excipients / Q000737:chemistry; D006943:Hyperglycemia / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D008297:Male; D008320:Maltose / Q000031:analogs & derivatives / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D003692:Delayed-Action Preparations; D005079:Excipients; D007004:Hypoglycemic Agents; D007328:Insulin; C459187:tetradecyl maltoside; D008320:Maltose