title: Pharmacokinetics of 125I-labeled insulin glargine (HOE 901) in healthy men: comparison with NPH insulin and the influence of different subcutaneous injection sites.
abstract: OBJECTIVE
  To determine the subcutaneous absorption rates and the appearance in plasma of 3 formulations of the long-acting human insulin analog insulin glargine (HOE 901) differing only in zinc content (15, 30, and 80 microg/ml).
  
  
  METHODS
  We conducted 2 studies. Study 1 compared the subcutaneous abdominal injection of 0.15 U/kg of 125I-labeled insulin glargine[15], insulin glargine[80], NPH insulin, and placebo. In study 2, 0.2 U/kg of insulin glargine[30] was injected into the arm, leg, and abdominal regions. Both studies had a randomized crossover design; each enrolled 12 healthy men, aged 18-50 years.
  
  
  RESULTS
  In study 1, the time in hours for 25% of the administered radioactivity to disappear after bolus subcutaneous injection (T75%) for NPH insulin indicated a significantly faster absorption rate compared with the 2 insulin glargine formulations (3.2 vs. 8.8 and 11.0 h, respectively P < 0.0001). Mean residual radioactivity with NPH insulin was also significantly lower at 24 h (21.9 vs. 43.8 and 52.2%, P < 0.0001). The calculated plasma exogenous insulin concentrations after NPH insulin were substantially higher than those with insulin glargine, reaching a peak within the first 6 h after administration before declining. Insulin glargine, however, did not exhibit a distinct peak. Weighted average plasma glucose concentration between 0 and 6 h was significantly lower after NPH compared with insulin glargine (P < 0.001). In study 2, there were no significant differences in the absorption characteristics of insulin glargine between the 3 injection sites (T75% = 11.9, 15.3, and 13.2 h for arm, leg, and abdomen, respectively) or in residual radioactivity at 24 h.
  
  
  CONCLUSIONS
  Subcutaneous absorption of insulin glargine is delayed compared with NPH insulin. There is little or no difference in the absorption rate of insulin glargine between the main subcutaneous injection sites.
authors.affiliation: University of Wales College of Medicine, Diabetes Research Unit, Academic Centre, Llandough Hospital, Penarth, South Glamorgan, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Owens
authors.forename: P A
authors.initials: PA
authors.lastname: Coates
authors.forename: S D
authors.initials: SD
authors.lastname: Luzio
authors.forename: J P
authors.initials: JP
authors.lastname: Tinbergen
authors.forename: R
authors.initials: R
authors.lastname: Kurzhals
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D049528:Insulin, Long-Acting; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D012016:Reference Values; D016037:Single-Blind Method
chemical_list: D007328:Insulin; D049528:Insulin, Long-Acting; D007457:Iodine Radioisotopes; D000069036:Insulin Glargine; D007336:Insulin, Isophane