Time-action profiles of novel premixed preparations of insulin lispro and NPL insulin.
OBJECTIVE
To study the pharmacodynamic properties of three premixed formulations of the rapid-acting insulin analog insulin lispro and its protamine-retarded preparation, neutral protamine lispro (NPL) insulin.


METHODS
In this open, single-center, euglycemic glucose clamp study, 30 healthy volunteers (12 women, 18 men) aged 27 +/- 2 years (mean +/- SD), whose BMI was 23.0 +/- 2.3 kg/m2, 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 activity decreased after subcutaneous injection of the mixtures with lower insulin lispro content; however, the time point of maximal and of early half-maximal metabolic activity was comparable among the three mixtures. 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 concentrations 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.
Heise
T
T
Department of Metabolic Diseases and Nutrition, World Health Organization Collaborating Center for Diabetes, Heinrich-Heine-University of Düsseldorf, Germany.
Weyer
C
C
Serwas
A
A
Heinrichs
S
S
Osinga
J
J
Roach
P
P
Woodworth
J
J
Gudat
U
U
Heinemann
L
L
D000328:Adult; D002096:C-Peptide / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D061268:Insulin Lispro; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D004364:Pharmaceutical Preparations; D013997:Time Factors
D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; D004364:Pharmaceutical Preparations; D007336:Insulin, Isophane; D005947:Glucose