title: A comparison of the steady-state pharmacokinetics and pharmacodynamics of a novel rapid-acting insulin analog, insulin glulisine, and regular human insulin in healthy volunteers using the euglycemic clamp technique.
abstract: Insulin glulisine is a new rapid-acting insulin analog. The aim of this study was to assess the glucodynamic efficacy of insulin glulisine compared with regular human insulin (RHI) using a manual euglycemic clamp technique. Steady-state pharmacokinetics of insulin glulisine, and its cardiac safety (ECG) and tolerability after intravenous administration, were also determined. This was a single center, randomized, open-label, two-way crossover study in healthy male subjects (n = 16). At the treatment visits subjects received an intravenous infusion of the study drug at a rate of 0.8 mU kg (-1) . min (-1) for 2 hours. Individual baseline glucose concentrations were targeted for euglycaemia and maintained with a manual adjusted 20 % glucose solution over the clamp period of a maximum 6 hours. A glulisine-specific antibody was used to quantify glulisine concentrations by radioimmunoassay, while a non-specific insulin antibody and C-peptide based correction for endogenous insulin was used to estimate exogenous human insulin (RHI). At steady state (90 - 120 min), insulin glulisine and RHI had equivalent glucose utilization (GIR-AUC (SS), 209 [corrected] mg . kg (-1) for glulisine, 214 [corrected] mg . kg (-1) for RHI) and infusion rates (GIR (SS), 7.0 and 7.2 [corrected] mg . kg (-1) . [corrected] min (-1) . kg (-1)). Both insulins also presented equal total glucose disposal (GIR-AUC (0 - clamp end), 995 and 1050 [corrected] mg . kg (-1)) and onset of activity within 20 min. Insulin glulisine and RHI showed parallel time concentration profiles with similar distribution and elimination, but the different antibodies employed for radioimmunoassay impeded a quantitative comparison. There were no noteworthy individual or within-group changes in cardiac repolarisation parameters measured by 12-lead ECG during insulin glulisine infusion. In conclusion, insulin glulisine and RHI show similar distribution and elimination profiles and equivalent glucodynamic efficacy on a molar, unit-per-unit basis.
authors.affiliation: Aventis Pharma Deutschland GmbH, Industriepark Höchst, 65926 Frankfurt am Main, Germany. Reinhard.Becker@aventis.com
authors.forename: R H A
authors.initials: RH
authors.lastname: Becker
authors.forename: A D
authors.initials: AD
authors.lastname: Frick
authors.forename: F
authors.initials: F
authors.lastname: Burger
authors.forename: H
authors.initials: H
authors.lastname: Scholtz
authors.forename: J H
authors.initials: JH
authors.lastname: Potgieter
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011994:Recombinant Proteins
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011994:Recombinant Proteins; C479079:insulin glulisine