Interindividual Variability in the Pharmacodynamic and Pharmacokinetic Characteristics of Recombinant Human Insulin and Insulin Aspart.

Abstract Purpose The present study compared the interindividual variability in the pharmacodynamic (PD) and pharmacokinetic (PK) properties of a short-acting recombinant human insulin to those of insulin aspart through manual euglycemic glucose clamp tests. Methods Sixty healthy Chinese male volunteers were randomly assigned to receive human insulin or insulin aspart, administered via SC injection (0.2 U/kg). For the evaluation of interindividual variability in PD and PK properties (glucose infusion rate [GIR], insulin concentration [INS]) through euglycemic clamp studies, %CVs were calculated, and PK/PD interindividual variability was compared between the 2 groups. Findings : The differences between the human insulin and insulin aspart groups in interindividual variabilities in total AUCs of the GIR (19% vs 21%) and INS (14% vs 17%) were not significant. The interindividual variabilities in AUC gir 0–120min, early Tmax50%, and AUC ins 0–120min were lower in the insulin aspart group than in the human insulin group (22% vs 44%, 21% vs 35%, and 22% vs 28%, respectively; all, P ˂ 0.05), while the interindividual variabilities in the AUCs of GIR120–600min and INS120–600min were higher with insulin aspart than with human insulin (29% vs 20%, 51% vs 30%; both, P ˂ 0.05). Implications The overall interindividual variability with insulin aspart was similar to that with recombinant human insulin. Yet insulin concentration and metabolic effect during the declining period were more variable with insulin aspart compared to human insulin in these healthy male subjects.