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Pharmacokinetics, tissue distribution and excretion of a novel long-acting human insulin analogue – recombinant insulin LysArg in rats
Xenobiotica ( IF 1.3 ) Pub Date : 2020-11-16 , DOI: 10.1080/00498254.2020.1847361
Tao Cui 1 , Yazhuo Li 1 , Zihong Wei 1 , Xingyan Zhang 2 , Wei Li 1 , Wei Zhou 3 , Jiangjie Lu 3 , Jing Li 3 , Xiulin Yi 1 , Yong Zeng 1 , Changxiao Liu 1 , Fengying Yan 1, 4
Affiliation  

Abstract

  1. As a novel long-acting recombinant human insulin analogue, it is necessary to carry out the preclinical research for insulin LysArg. The purpose of this study was to characterise the pharmacokinetic, tissue distribution and excretion of insulin LysArg and provide a reference for its development.

  2. Three methods were used to measure the content of insulin LysArg in biological samples after a single subcutaneous administration in rats, including radioassay, radioassay after precipitation with TCA and separation by HPLC.

  3. After Subcutaneous administration of recombinant insulin LysArg 1, 2, 4 U/kg in rats, it showed both Cmax and AUC0–t were positively correlated with the dose. In the meanwhile, after a single subcutaneous administration of recombinant insulin LysArg at 2 U/kg in rats, the amount of radioactivity in most organs was highest at 1.5 h and then decreased gradually, no accumulation was found. The highest level of insulin LysArg was observed in the kidney. Like other macromolecules, insulin LysArg was mainly excreted from urine.

  4. The study fully illustrated the pharmacokinetic pattern of insulin LysArg, provided valuable informations to support its further development about safety and toxicology.



中文翻译:

新型长效人胰岛素类似物重组胰岛素LysArg在大鼠体内的药代动力学,组织分布和排泄

摘要

  1. 作为一种新型的长效重组人胰岛素类似物,有必要进行LysArg胰岛素的临床前研究。这项研究的目的是表征LysArg胰岛素的药代动力学,组织分布和排泄,并为其发展提供参考。

  2. 在大鼠皮下单次给药后,使用三种方法测量生物样品中胰岛素LysArg的含量,包括放射分析,TCA沉淀后的放射分析和HPLC分离。

  3. 在大鼠皮下注射重组胰岛素LysArg 1、2、4 U / kg后,显示C max和AUC 0–t均与剂量呈正相关。同时,在大鼠皮下单次皮下注射重组胰岛素LysArg 2 U / kg后,大多数器官的放射性量在1.5 h最高,然后逐渐降低,未发现积累。在肾脏中观察到最高水平的LysArg胰岛素。像其他大分子一样,胰岛素LysArg主要从尿液中排出。

  4. 该研究充分说明了胰岛素LysArg的药代动力学模式,为支持其在安全性和毒理学方面的进一步发展提供了有价值的信息。

更新日期:2020-11-16
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