Pharmacokinetics, Pharmacodynamics and Bioequivalence of Test Insulin Glargine versus Reference Preparation (Lantus®) in Healthy Male Volunteers—by Euglycemic Clamp Technique

Aim: To evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and bioequivalence of two insulin glargine preparations in Chinese healthy male subjects. Methods Randomized, open, two-sequence, four-period, single-dose, crossover design was applied in this study. A total of 40 healthy Chinese men were recruited and randomly divided into RTRT or TRTR groups. Pharmacodynamic parameters of the preparations were measured by a 24h euglycemic clamp test. Plasma insulin glargine concentration and C-peptide were collected during the trial and analyzed by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) and enzyme-linked immunosorbent assay (ELISA). SAS V9.4 was used for calculation of pharmacodynamic and pharmacokinetic parameters and the equivalence of the two preparations. Results The average concentration of C-peptide of each sequence was lower than the baseline. PK parameters c max of the test and the reference preparation insulin glargine were 0.580 and 0.614 ng·mL − 1 , and the AUC 0 − 24h were 9.782 and 10.436 h·ng·mL − 1 , respectively. PD parameters GIR max were 42.748 and 45.279 mg·kg − 1 ·min − 1 , AUC GIR,0−24h were 2.924 and 3.096 h·mg·kg − 1 ·min − 1 , respectively. There was no clinically significant adverse reaction observed during the experiment. Conclusion The quality of the glucose clamp in this study is superior. The test insulin Glargine was bioequivalent with the reference preparation.