[The Pharmacokinetics, Pharmacodynamics and Bioequivalence of Insulin Aspart Produced by the United Laboratories Evaluated by Euglycemic Clamp Study]

Abstract

Objective: To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of a rapid-acting insulin analog-insulin aspart (the tested formulation) which was manufactured by The United Laboratories and to evaluate the bioequiavailability to the reference formulation (NovoRapid ^®) produced by Novo Nordisk in Chinese healthy volunteers.

Methods: A total of 24 male healthy volunteers were recruited from February to April 2016 to participant in this before-after, single dose, and randomized crossover study. And the experimental observation was conducted on 2 test days respectively with a between-period from 7 to10 d. According to a random number table, the volunteers were divided into group A or B, group A was administrated with tested insulin aspart (IAsp) for the first time and reference NovoRapid ^® for the second time and group B had the revered order differed from group A. The PK/PD of these insulin analogs were estimated by euglycemic clamp study.

Results: The relative biological effectiveness (reflecting gloucose-lowing effect) and bioavailability on behalf of plasma-drug concentration were 98.3±18.8% and 97.3%±8.3% respectively. For PK parameters, the 90% confidence interval ( CI) of peak plasma insulin concentration ( C _max) and area under the curve of insulin aspart concentration from 0 to 10 hours ( AUC _{IAsp, 0-10 h}) of IAsp were 88.8%-106% (equivalent range 70%-143%) and 94.0%-100% (equivalent range 80%-125%) respectively; for PD parameters, the 90% CI of the maximum glucose infusion rate ( GIR _max) and AUC _{GIR, 0-10 h} were 95.5%-113% (equivalent range 70%-143%) and 89.9%-104% (equivalent range 80%-125%) respectively, which indicated that IAsp and NovoRapid® was bioequivalent. One of the subjects discovered hyperuricemia without clinical symptoms and the rest had no clinically significant abnormalities in the safety indexes before and after the tests. No hypoglycemic events, allergic reactions, or local injection adverse reaction occurred in this trial.

Conclusion: The tested IAsp has comparable relative bioavailability to the reference NovoRapid ^®.

Keywords: Bioequivalence; Euglycemic clamp; Insulin analogs; Phannacodynamics; Pharmacokinetics.