Zhu Mingxue, Chen Yuan, Wan Lei, Li Zhongping, Pu Junliang, Tang Chengyong
Phase I Clinical Trial Center, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical University, Chongqing, China.
Front Pharmacol. 2025 Feb 25;16:1533548. doi: 10.3389/fphar.2025.1533548. eCollection 2025.
There are approximately 537 million adults with diabetes worldwide, and insulin still plays an important role in its treatment. However, the long-term use of insulin imposes a significant financial burden on patients. This study aims to explore the pharmacokinetic (PK)/ pharmacodynamic (PD) parameters of generic premixed insulin lispro 25 (25% insulin lispro and 75% protamine zinc lispro) and evaluate the bio-equivalence between generic and brand-name preparations to reduce medical costs while ensuring the effectiveness and safety of treatment. This is a single-center, randomized, open-label, two-period, crossover study. This study recruited 52 healthy volunteers and randomly divided them into two sequences to receive either the test (T) preparation or the reference (R) preparation in each period (Chinese Drug Trial Identifier: CTR20202288, URL: http://www.chinadrugtrials.org.cn). The C-peptide and plasma concentration of lispro 25 were analyzed using ELISA and high-performance liquid chromatography, respectively. A euglycemic clamp was used to measure the glucose infusion rate (GIR). The main PK parameters (AUC and C) and PD parameters (GIR and GIR) and the evaluation of bioequivalence were calculated using WinNonlin 8.3.1. The quality of the clamp was approved by stable blood glucose and inhibited C-peptide levels. For PK parameters, the C values of the T and R preparations were 1.40 ± 0.452 and 1.36 ± 0.418 ng·mL, respectively, and the AUC values were 497 ± 107 and 510 ± 86.2 ng h·mL, respectively. For PD parameters, GIR values were 4.47 ± 2.12 and 4.12 ± 1.81 mg kg·min, and AUC values were 2,994 ± 1,232 and 2,994 ± 941 mg h·kg·min for T and R, respectively. The 90% confidence intervals (CIs) for the geometric mean ratio (test/reference) of the main PK parameters (AUC and C) and PD parameters (GIR and GIR) in both cohorts were within the range of 80%-125%. Furthermore, there was no significant hypoglycemia and serious adverse events (SAEs) observed in this study. Bio-equivalence between insulin lispro (R) (Humalog25) and insulin lispro (T) was demonstrated, with both showing good tolerance in healthy Chinese volunteers. The results provide evidence supporting the interchangeability of different drug formulations and offer more options for clinical drug use.
全球约有5.37亿成年糖尿病患者，胰岛素在其治疗中仍发挥着重要作用。然而，长期使用胰岛素给患者带来了沉重的经济负担。本研究旨在探索通用型赖脯胰岛素25（25%赖脯胰岛素和75%精蛋白锌赖脯胰岛素）的药代动力学（PK）/药效学（PD）参数，并评估通用型制剂与品牌制剂之间的生物等效性，以降低医疗成本，同时确保治疗的有效性和安全性。这是一项单中心、随机、开放标签、两期交叉研究。本研究招募了52名健康志愿者，随机分为两个序列，在每个时期分别接受试验（T）制剂或参比（R）制剂（中国药物临床试验标识符：CTR20202288，网址：http://www.chinadrugtrials.org.cn）。分别采用酶联免疫吸附测定法（ELISA）和高效液相色谱法分析赖脯胰岛素25的C肽和血浆浓度。采用正常血糖钳夹技术测量葡萄糖输注速率（GIR）。使用WinNonlin 8.3.1计算主要PK参数（AUC和C）和PD参数（GIR和GIR）并评估生物等效性。钳夹质量通过稳定的血糖和抑制的C肽水平得到验证。对于PK参数，T制剂和R制剂的C值分别为1.40±0.452和1.36±0.418 ng·mL，AUC值分别为497±107和510±86.2 ng h·mL。对于PD参数，T制剂和R制剂的GIR值分别为4.47±2.12和4.12±1.81 mg kg·min，AUC值分别为2994±1232和2994±941 mg h·kg·min。两个队列中主要PK参数（AUC和C）和PD参数（GIR和GIR）的几何平均比（试验/参比）的90%置信区间（CI）在80%-125%范围内。此外，本研究中未观察到明显低血糖和严重不良事件（SAE）。证明了赖脯胰岛素（R）（优泌乐25）和赖脯胰岛素（T）之间的生物等效性，两者在健康中国志愿者中均显示出良好的耐受性。研究结果为不同药物剂型的互换性提供了证据支持，为临床用药提供了更多选择。
