A Comparison of Pharmacokinetics and Pharmacodynamics of Biphasic Insulin Aspart 30, 50, 70 and Pure Insulin Aspart: A Randomized, Quadruple Crossover Study

Abstract

The purpose of this study was to evaluate pharmacokinetic and pharmacodynamic profiles of pure insulin aspart and three different formulations of insulin aspart and protaminated insulin aspart: biphasic insulin aspart 30 (BIAsp30), biphasic insulin aspart 50 (BIAsp50) and biphasic insulin aspart 70 (BIAsp70). Nineteen type 1 diabetes patients received individually identical doses of the four different insulin aspart preparations on 4 separate days in this randomized crossover study. Having achieved overnight stable blood glucose control by intravenous infusions of human insulin, one of the trial insulins was injected subcutaneously and a standard meal was given in the morning. Plasma glucose and serum insulin aspart were recorded the following 12 hr. During the first 4 hr after injection with the trial insulin, the area under the curve for levels of insulin aspart (AUC(ins)) was significantly higher during insulin aspart treatment as compared to the other three insulin treatments, followed by BIAsp70, BIAsp50 and BIAsp30 (P < 0.05). Over the last 4 hr, the AUC(ins) for BIAsp30 was significantly higher as compared to the other insulin preparations (P < 0.05). By contrast, during the initial 4 hr, the area under the curve for levels of glucose (AUC(glu)) was highest after injection with BIAsp30 compared to the other three treatments (P < 0.05), while during the last 4 hr the highest AUC(glu) was seen following insulin aspart (P < 0.05). We conclude that when insulin aspart is pure or formulated with protamine in three different ratios, the pharmacokinetic profiles are readily distinguishable. These differences in pharmacokinetics are reflected in the pharmacodynamic profiles.