title: Pharmacodynamic and pharmacokinetic properties of a premixed 85/15 human insulin preparation.
abstract: BACKGROUND
  Many patients with diabetes use mixtures of fast-acting (regular human) insulin and intermediate-acting (neutral protamine Hagedorn [NPH]) insulin to control their blood glucose levels. Premixed insulin is available in a 70%/30% mixture and a 50%/50% mixture of NPH/regular human insulin. For some patients, however, a premixed formulation containing > or =30% regular human insulin can provide too much fast-acting insulin, potentially causing an increased risk for hypoglycemia in the early hours after injection.
  
  
  OBJECTIVE
  The pharmacokinetic and pharmacodynamic properties of a premixed formulation of 85% NPH insulin and 15% regular human insulin (85/15) were compared with those of a premixed 70%/30% NPH/regular human insulin preparation and 100% NPH insulin.
  
  
  METHODS
  A 12-hour euglycemic clamp approach was used to assess glucose-lowering effects and serum insulin levels in 36 healthy male volunteers in a single-dose (0.5 U/kg), randomized, double-blind, 3-period, crossover study.
  
  
  RESULTS
  From 0 to 8 hours after injection, the glucose-lowering effects and serum insulin levels for the 85/15 premixed insulin preparation were significantly greater than those for NPH insulin (P < or = 0.05) but significantly less than those for the 70/30 premixed insulin preparation. The mean (+/- SEM) maximum glucose infusion rate (GIRmax) was 8+/-0.6 mg/(min x kg) for the 85/15 preparation, 7+/-0.6 mg/(min x kg) for NPH, and 9+/-0.6 mg/(min x kg) for the 70/30 preparation, with time to peak GIR (tmax(GIR)) occurring at 313, 360, and 272 minutes, respectively. Time to peak insulin levels did not differ significantly for the 3 preparations, but maximum serum insulin concentration (Cmax(ins)) was significantly different between the groups (70/30 premix: 54+/-2.2 microU/mL; 85/15 premix: 44+/-2.4 microU/mL; NPH: 35+/-1.7 microU/mL). Glucodynamic effect and serum insulin levels did not differ significantly among preparations during the interval from 8 to 12 hours after injection. Mean serum C-peptide levels ranged from -0.6 to 1.0 ng/mL for each preparation during the 12-hour period after injection.
  
  
  CONCLUSIONS
  The 85/15 premixed insulin preparation demonstrated clinical pharmacokinetic and pharmacodynamic properties that were intermediate between, and significantly different from, those of NPH insulin and the 70/30 premixed insulin preparation.
authors.affiliation: Veterans Affairs San Diego Healthcare System, California 92161, USA. smudaliar@vapop.ucsd.edu
authors.forename: S R
authors.initials: SR
authors.lastname: Mudaliar
authors.forename: P
authors.initials: P
authors.lastname: Mohideen
authors.forename: S C
authors.initials: SC
authors.lastname: Baxi
authors.forename: M
authors.initials: M
authors.lastname: Joyce
authors.forename: D A
authors.initials: DA
authors.lastname: Armstrong
authors.forename: P
authors.initials: P
authors.lastname: Strange
authors.forename: R R
authors.initials: RR
authors.lastname: Henry
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007328:Insulin / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male
chemical_list: D001786:Blood Glucose; D007328:Insulin