Abstract：
E3112 is a recombinant human hepatocyte growth factor which is under development for the treatment of acute liver failure. Pharmacokinetics (PK) evaluation in experimental animals is important and thus a simple assay for the determination of E3112 in rat and monkey serum has been validated using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. E3112 in rat and monkey serum was quantifiable from 0.313 ng/mL to 15.0 ng/mL without prozone effects. Dilution integrity enabled accurate assay up to 500,000-fold dilution. Accuracy and precision were within the acceptance criteria. PK of E3112 was investigated after intravenous administration to rats and monkeys. PK of E3112 was similar between male and female animals in both species. Nonlinear PK of E3112 was observed in rats after intravenous bolus dose at 1-100 mg/kg while nonlinear PK was not significant in monkeys after intravenous infusion at 0.5-25 mg/kg. These findings suggest that the assay of E3112 in serum using a commercially available ELISA kit was validated and successfully applied to PK studies in rats and monkeys.
摘要：
E3112是一种重组人肝细胞生长因子，正在开发用于治疗急性肝衰竭。实验动物中的药代动力学（PK）评估很重要，因此已使用市售的酶联免疫吸附测定（ELISA）试剂盒验证了用于测定大鼠和猴血清中E3112的简单测定法。大鼠和猴血清中的E3112可从0.313ng/mL定量到15.0ng/mL，而没有前区效应。稀释完整性使得能够进行高达500,000倍稀释的准确测定。准确度和精密度在验收标准内。在静脉内给予大鼠和猴后研究E3112的PK。E3112的PK在两个物种的雄性和雌性动物之间相似。在1-100mg/kg的静脉推注剂量后，在大鼠中观察到E3112的非线性PK，而在0.5-25mg/kg的静脉输注后，在猴子中非线性PK不明显。这些发现表明，使用市售ELISA试剂盒对血清中E3112的测定得到了验证，并成功地应用于大鼠和猴子的PK研究。
