Priclinical Pharmacokinetics Studies Of IL2-HSA Fusion Protein

Based on the Biological engineering research of Academy of Military Sciences have developed a new drug human serum albumin and Interleukin-2 fusion protein?IL2-HSA fusion protein?in rats/mices and cynomolgus monkeys in vivo pharmacokinetic studies,IL2-HSA fusion protein pharmacokinetics provide objective and accurate evaluation,but also for clinical research.The design and optimization of dosage regimen provides a strong theoretical basis.This test uses a combination of radioisotope ¹²⁵I labeling TCA precipitation method,as well as gel high performance liquid chromatography?SHPLC?study of IL2-HSA fusion protein in rats in vivo absorption,distribution,metabolism and excretionprocesses.Determination of double-antibody sandwich method in serum samples of cynomolgus monkeys with the concentration of IL2-HSA fusion protein to study the IL2-HSA fusion protein in the crab-eating monkeys in vivo metabolic processes.The results show that,SD rats were SC injected ¹²⁵I-IL2-HSA fusion protein,the terminal elimination phase half-life of total radioactivity and TCA precipitated were 15.5 ± 1.8 h and 16.3 ±2.5 h.¹²⁵I-IL2-HSA fusion protein in the Balb/c mices are widely distributed,non-specific targeting,the excretion primarily through urine excretion.Monkeys sc 0.05?0.15 and 0.45 mg·kg-1 IL2-HSA fusion protein,the peak of the time is about 8h,and the peak of concentrations were 352±9.8?456.0±160.9 ?2,074.2±334.2 ng·mL-1,then began a slow process of elimination.The dose ratio of the three groups is 1:3:9;and the.maxium of the concentration of the drug is 1:12.9:58.9.it is a nonlinear pharmacokinetics characters.Monkeys iv inject 0.15 mg·kg-1 IL2-HSA fusion protein,the concentration of injected 5 minute is 4,998.8±602.0 ng·mL-1,then reduced to 48 h to background level.The absolute bioavailability of SC inject 0.15 mg·kg-1 IL2-HSA fusion protein is 23.1%.After monkeys SC inject equal mole IL-2?0.15 mg·kg-1 IL2-HSA fusion protein,0.03 mg·kg-1 IL-2?,the terminal elimination phase half-life are 5.8±1.8 and 0.7±0.3 h.¹²⁵I-IL2-HSA fusion protein in the Balb/c mices are widely distributed,non-specific targeting,the excretion primarily through urine excretion.¹²⁵I-IL2-HSA fusion protein does not bind with the plasma protein of SD rat.;it is a nonlinear pharmacokinetics characters on the experiment of monkeys.The absolute bioavailability of SC inject IL2-HSA fusion protein is 23.1%.After multiple SC injecting IL2-HSA fusion protein,it produced anti-drug antibody in the monkeys.Comparing with IL-2 on the pharmacokinetics.the rates of metabolism is lower than IL-2,and the half-life is longer than IL-2.