Pharmacodynamics and pharmacokinetics of a new type of recombinant insulin Lisargine injection

Abstract

Background Recombinant insulin Lisargine is a new type of insulin. In this study, we aimed to compare its pharmacodynamic (PD) and pharmacokinetic (PK) with Lantus. Methods The PD test was performed by exploring the effect of single administration on blood glucose of normal rats and STZ-induced diabetic rats, and the effect of multiple administrations on blood glucose of STZ-induced diabetic rats. Further PD tests include receptor affinity test, receptor autophosphorylation test and adipocyte glucose uptake test. Four IU and 8 IU per dog Lisargine was used for PK test, insulin was measured and area under curve (AUC) was calculated. Results With single injection, Lisargine 1.5 IU/kg had significant hypoglycemic effects at 1 and 2 h, similar to that of Lantus. Lisargine 5 IU/kg and 10 IU/kg lowered the blood glucose of STZ-induced diabetic rats at 1, 2, 4 & 6 h significantly. With multiple injections, Lantus lowered blood glucose at 2, 4 & 6 h, Lisargine 2.5 IU/kg, 5 IU/kg, and 10 IU/kg lowered blood glucose at 2 & 4 h significantly, compared with vehicle. There was no difference for receptor affinity test, receptor autophosphorylation test and adipocyte glucose uptake test between Lisargine and Lantus. The PK of Lisargine and Lantus of healthy Beagle dogs was very similar. Conclusions This animal study demonstrated that PK and PD of Lisargine and Lantus were similar, suggesting the bioequivalence of these products.

Analysis of a novel insulin lisargine at the molecular level using X-ray crystallography and biophysical techniques

“…Insulin lisargine is a novel insulin analogue used for the treatment of diabetes 1 . It exhibits structural modi cations compared to human insulin, where asparagine at position B3 in the A chain is replaced by lysine, and lysine and arginine are introduced at positions B31 and B32 in the B chain, respectively.…”