Pharmacokinetics, tissue distribution and excretion of a novel long-acting human insulin analogue – recombinant insulin LysArg in rats

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 C_max and AUC_0–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.

Keywords:

• Recombinant insulin LysArg
• pharmacokinetics
• distribution
• excretion
• radioisotope tracing

Disclosure statement

Mr. Wei Zhou, Jiangjie Lu, Ms. Jing Li are employees of Hefei Tianmai Biotechnology Development Co. Ltd. Other authors declare no conflict of interest.

Additional information

Funding

The authors are grateful for financial support of National Key Research and Development Program [2016YFE0121400], National Major Project in Drug Innovation [2012ZX09304-002] and CAMS Innovation Fund for Medical Sciences [Grant No. 2019-I2M-5-020].