A comparison of pharmacokinetics and pharmacodynamics of insulin aspart, biphasic insulin aspart 70, biphasic insulin aspart 50, and human insulin: a randomized, quadruple crossover study.

BACKGROUND We compared the pharmacokinetic and pharmacodynamic profiles of insulin aspart, biphasic insulin aspart 70 (BIAsp70) and 50 (BIAsp50) (containing 70% and 50% rapid-acting insulin aspart, respectively), and soluble human insulin under experimental conditions. SUBJECTS AND METHODS In this randomized, four-period crossover study, 19 type 1 diabetes patients received subcutaneous injections of identical doses (0.2 U/kg) of insulin aspart, BIAsp70, or BIAsp50 immediately before a standardized meal or human insulin 30 min before meal. Plasma glucose and serum insulin were measured for 12 h postprandially. RESULTS The pharmacokinetic and pharmacodynamic profiles of human insulin differed from those of insulin aspart, BIAsp70, and BIAsp50. The three different aspart preparations had easily distinguishable features with regard to onset and duration of action. Insulin aspart preparations were, on average, absorbed twice as fast as human insulin. In the initial phases (0-4 h and 0-6 h), the insulin area under the concentration-time curve (AUC(ins)) was significantly higher during insulin aspart treatment compared with the others, whereas insulin aspart had a significantly lower AUC(ins) over the last 6 h (P<0.05). BIAsp70 and BIAsp50 provided insulin coverage comparable to that of human insulin over the last 6 h. Insulin aspart had the most pronounced onset of action and the shortest duration. Comparing with insulin aspart and BIAsp70, BIAsp50 revealed a closer treatment ratio to human insulin on pharmacodynamic end points. CONCLUSIONS BIAsp70 and BIAsp50 injected immediately before a meal are at least as effective as human insulin injected 30 min earlier in controlling postprandial glycemic excursions. BIAsp50 showed the greatest similarity to human insulin with regard to pharmacokinetic and pharmacodynamic profiles.