Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China.
Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China.
Clin Ther. 2021 Mar;43(3):594-601.e1. doi: 10.1016/j.clinthera.2021.01.008. Epub 2021 Feb 5.
The present study compared the interindividual variability in the pharmacodynamic (PD) and pharmacokinetic (PK) properties of a short-acting recombinant human insulin to those of insulin aspart through manual euglycemic glucose clamp tests.
Sixty healthy Chinese male volunteers were randomly assigned to receive human insulin or insulin aspart, administered via SC injection (0.2 U/kg). For the evaluation of interindividual variability in PD and PK properties (glucose infusion rate [GIR], insulin concentration [INS]) through euglycemic clamp studies, %CVs were calculated, and PK/PD interindividual variability was compared between the 2 groups.
The differences between the human insulin and insulin aspart groups in interindividual variabilities in total AUCs of the GIR (19% vs 21%) and INS (14% vs 17%) were not significant. The interindividual variabilities in AUCgir, early T, and AUCins were lower in the insulin aspart group than in the human insulin group (22% vs 44%, 21% vs 35%, and 22% vs 28%, respectively; all, P ˂ 0.05), while the interindividual variabilities in the AUCs of GIR and INS were higher with insulin aspart than with human insulin (29% vs 20%, 51% vs 30%; both, P ˂ 0.05).
The overall interindividual variability with insulin aspart was similar to that with recombinant human insulin. Yet insulin concentration and metabolic effect during the declining period were more variable with insulin aspart compared to human insulin in these healthy male subjects.
本研究通过手动正葡萄糖钳夹试验比较了短效重组人胰岛素和门冬胰岛素的药效学（PD）和药代动力学（PK）个体间变异性。
60 名健康中国男性志愿者随机分为接受人胰岛素或门冬胰岛素皮下注射（0.2 U/kg）组。为了通过正葡萄糖钳夹研究评估 PD 和 PK 个体间变异性（葡萄糖输注率[GIR]，胰岛素浓度[INS]），计算了%CV，并比较了两组之间的 PK/PD 个体间变异性。
GIR（19%比 21%）和 INS（14%比 17%）的总 AUC 个体间变异性在人胰岛素组和门冬胰岛素组之间差异无统计学意义。门冬胰岛素组 AUCgir、早期 T 和 AUCins 的个体间变异性低于人胰岛素组（22%比 44%、21%比 35%和 22%比 28%；均 P ˂ 0.05），而门冬胰岛素组的 GIR 和 INS AUC 的个体间变异性高于人胰岛素组（29%比 20%、51%比 30%；均 P ˂ 0.05）。
门冬胰岛素的总体个体间变异性与人胰岛素相似。然而，与重组人胰岛素相比，在这些健康男性受试者中，门冬胰岛素的胰岛素浓度和代谢效应在下降期的变异性更大。
