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

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)center dot 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), 214 mg center dot kg(-1) for glulisine, 209 mg center dot kg(-1) for RHI) and infusion rates (GIR(SS), 1050 and 995 mg center dot min(-1)center dot kg(-1)). Both insulins also presented equal total glucose disposal (GIR-AUC(0-clamp end), 1050 and 995 mg center dot 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.