Pharmacokinetics and Pharmacodynamics of insulin Lispro25 versus the original preparation (Humalog®25) in Chinese Healthy Male Volunteers

Mingxue Zhu Yuan Cheng Lei Wan Zhongping Li Junliang Pu Chengyong Tang ^*

• Bishan hospital of Chongqing Medical University, Chongqing, China

Background: There are approximately 537 million adults with diabetes worldwide and insulin still plays an important role in its treatment.. However, long-term use of insulin imposes a significant financial burden on patients. This study aims to explore the PK/PD of generic premixed insulin Lispro 25(25% Insulin Lispro, 75%protamine zinc Lispro) and evaluate the bio-equivalence between generic and brand-named preparations so that we can Reduce medical costs while ensuring the effectiveness and safety of treatment. Research design and method: This is a single-center, randomized, open-label, two-period, crossover study recruited 52 healthy volunteers who were randomly divided into two sequences and received the test preparation or reference preparation in each period respectively (Chinese Drug Trial Identifier: CTR20202288, URL: http://www.chinadrugtrials.org.cn). The C-peptide and plasma concentration of Lispro 25 were analyzed by ELISA and high-performance liquid chromatography respectively. The euglycemic clamp was used to measure the GIR value. The main PK (AUC0-t, Cmax) , PD (GIRmax, GIRAUC0-t) parameters and the evaluation of bioequivalence were calculated by WinNonlin 8.3.1. Results: The quality of the clamp was approved by stable blood glucose and inhibited C-peptide level. For PK parameters, Cmax of the T and R preparation were 1.40±0.452 and 1.36±0.418 ng• mL-1, and the AUC0-24h were 497±107and 510±86.2ng• h• mL-1 respectively. For PD parameters, GIRmax were 4.47±2.12 and 4.12±1.81mg• kg• min-1 and AUCGIR0-24h were 2994±1232 and 2994±941mg• h• kg• min-1 for T and R, respectively. The 90%CIs for the geometric mean ratio (test/reference) of main PK (AUC0-t, Cmax) and PD (GIRmax, GIRAUC0-t)parameters in both cohorts were within the range of 80% to 125%. Besides, there was no significant hypoglycemia and SAE observed in this study. Conclusion: The bio-equivalence between insulin lispro (R) (Humalog®25) and insulin lispro (T)has been demonstrated and also showed a good tolerance in Chinese health volunteers. The results provide evidence of the interchangeability of different drug formulations and more options for clinical drug use.