TIME-ACTION PROFILES OF NOVEL PREMIXED PREPARATIONS OF INSULIN LISPROAND NPL INSULIN

OBJECTIVE -To study the pharmacodynamic properties of three premixed f ormulations of the rapid-acting insulin analog insulin lispro and its protamine-retarded preparation, neutral protamine lispro (NPL) insulin . RESEARCH DESIGN AND METHODS -In this open, single-center, euglycemic glucose clamp study, 30 healthy volunteers (12 women, 18 men) aged 27 +/- 2 years (mean I SD), whose BMI was 23.0 +/- 2.3 kg/m(2), received subcutaneous injections of 0.3 U/kg body wt of insulin mixture (high- mixture 75/25, mid-mixture 50/50, or low-mixture 25/75 insulin lispro/ NPL insulin), insulin lispro, or NPL insulin on one of the five study days in randomized order. Glucose infusion rates were determined over a period of 24 h after administration. RESULTS -Maximal metabolic acti vity decreased after subcutaneous injection oi. the mixtures with lowe r insulin lispro content; however, the time point of maximal and of ea rly half-maximal metabolic activity was comparable among the three mix tures. Higher proportions of insulin lispro resulted in higher values for area under the curve within the first 360 min after injection and a more rapid decline to late half-maximal activity Serum insulin conce ntrations showed a similar pattern. CONCLUSIONS -This study shows that the pharmacodynamic and pharmacokinetic properties of insulin lispro are preserved in stable mixtures with NPL insulin.