title: Absorption kinetics and action profiles of subcutaneously administered insulin analogues (AspB9GluB27, AspB10, AspB28) in healthy subjects.
abstract: OBJECTIVE
  The subcutaneous absorption and resulting changes in plasma insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations after subcutaneous bolus injection of three soluble human insulin analogues (AspB9GluB27, monomeric; AspB28, mixture of monomers and dimers; and AspB10, dimeric) and soluble human insulin were evaluated.
  
  
  METHODS
  Fasting healthy male volunteers (n = 7) were studied on five occasions 1 wk apart randomly receiving 0.6 nmol.kg-1 s.c. 125I-labeled AspB10 or soluble human insulin (Novolin R, Novo, Copenhagen); 1st study and 0.6 nmol.kg-1 s.c. 125I-labeled AspB28, AspB9GluB27 or soluble human insulin (2nd study). Residual radioactivity at the injection site was measured over 8 h with frequent venous sampling for plasma immunoreactive insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations.
  
  
  RESULTS
  The three analogues were absorbed 2-3 times faster than human insulin. The mean +/- SE time to 50% residual radioactivity was 94 +/- 6 min for AspB10 compared with 184 +/- 10 min for human insulin (P less than 0.001), 83 +/- 8 min for AspB28 (P less than 0.005), and 63 +/- 9 min for AspB9GluB27 (P less than 0.001) compared with 182 +/- 21 min for human insulin. delta Peak plasma insulin analogue levels were significantly higher after each analogue than after human insulin (P less than 0.005). With all three analogues, the mean hypoglycemic nadir occurred earlier at 61-65 min postinjection compared with 201-210 min for the reference human insulins (P less than 0.005). The magnitude of the hypoglycemic nadir was greater after AspB9GluB27 (P less than 0.05) and AspB28 (P less than 0.001) compared with human insulin. There was a significantly faster onset and offset of responses in C-peptide and intermediary metabolite levels after the analogues than after human insulin (P less than 0.05).
  
  
  CONCLUSIONS
  The rapid absorption and biological actions of these analogues offer potential therapeutic advantages over the current short-acting neutral soluble insulins.
authors.affiliation: Department of Medicine, University of Wales College of Medicine, Cardiff, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Kang
authors.forename: J
authors.initials: J
authors.lastname: Brange
authors.forename: A
authors.initials: A
authors.lastname: Burch
authors.forename: A
authors.initials: A
authors.lastname: Vølund
authors.forename: D R
authors.initials: DR
authors.lastname: Owens
mesh_terms: D020155:3-Hydroxybutyric Acid; D000328:Adult; D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D005990:Glycerol / Q000097:blood; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D007773:Lactates / Q000097:blood; D008297:Male; D008657:Metabolic Clearance Rate; D011972:Receptor, Insulin / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D012016:Reference Values; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D006885:Hydroxybutyrates; D007328:Insulin; D007773:Lactates; D011994:Recombinant Proteins; D011972:Receptor, Insulin; D000409:Alanine; D005990:Glycerol; D020155:3-Hydroxybutyric Acid