Insulin aspart in a 30/70 premixed formulation. Pharmacodynamic properties of a rapid-acting insulin analog in stable mixture.
OBJECTIVE
To study the pharmacodynamic properties of a 30/70 premixed formulation of the rapid-acting insulin analog insulin aspart (B28Asp) and its protamine-retarded preparation (30/70 IA) in comparison with a respective mixture of soluble human insulin and NPH insulin (30/70 HI).


METHODS
In this single-center double-blind euglycemic glucose-clamp study, 24 healthy male volunteers (age, 26 +/- 2 years; BMI, 23.7 +/- 1.7 kg/m2) received single subcutaneous injections of 0.3 U/kg body wt of either 30/70 IA or 30/70 HI on 2 study days in randomized order. Glucose infusion rates (GIRs) were determined over a 24-h period after administration.


RESULTS
The injection of 30/70 IA resulted in an earlier onset and more pronounced peak of action (tmax, 127 +/- 24 min; GIRmax 9.7 +/- 2.3 mg.kg-1.min-1) than 30/70 HI (tmax, 185 +/- 52 min; GIRmax, 7.4 +/- 1.7 mg.kg-1.min-1_ (P < 0.001). The metabolic activity of 30/70 IA (measured as the sum of the glucose infused) within the first 4 h after injection was 37% greater than that of 30/70 HI (P < 0.0001), while the total metabolic potencies over 24 h of both preparations were comparable.


CONCLUSIONS
The 30/70 premixed formulation of insulin aspart shows a significantly greater metabolic effect in the first 4 h after subcutaneous injection than the 30/70 mixture of human insulin. Insulin aspart retains its pharmacodynamic properties in a premixed 30/70 formulation.
Weyer
C
C
Department of Metabolic Diseases and Nutrition, World Health Organization Collaborating Center for Diabetes Treatment and Prevention, Heinrich Heine University of Düsseldorf, Germany.
Heise
T
T
Heinemann
L
L
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D015309:Glucose Clamp Technique; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D061267:Insulin Aspart; D008297:Male; D008657:Metabolic Clearance Rate; D011897:Random Allocation; D013997:Time Factors
D001786:Blood Glucose; D004338:Drug Combinations; D007328:Insulin; D061267:Insulin Aspart