Supplementary Material for: Pharmacokinetics and Pharmacodynamics following Intravenous Administration of Recombinant Human Hepatocyte Growth Factor in Rats with Renal Injury

<b><i>Background/Aim:</i></b> Hepatocyte growth factor (HGF) plays a role in the regeneration and protection of the kidney, but little information is available concerning the pharmacokinetics of therapeutic treatment with HGF. In this study, HGF was administered after the onset of renal injury, and pharmacokinetic analysis was performed simultaneously with an efficacious dose. <b><i>Methods:</i></b> For the study of pharmacodynamics, recombinant human HGF was intravenously administered to rats with glycerol-induced acute kidney injury (AKI). In the pharmacokinetic study, rats subjected to glycerol injection or renal ischemia-reperfusion were used as models of AKI, and rats subjected to 5/6 nephrectomy were used as models of chronic kidney disease (CKD). <b><i>Results:</i></b> After intravenous administration of HGF at doses of 0.5-2.0 mg/kg, the elevation of blood urea nitrogen was suppressed, indicating that HGF had a pharmacodynamic effect. However, no significant difference was seen in the pharmacokinetic parameters such as clearance, distribution volume and half-life between the normal, AKI and CKD groups. <b><i>Conclusion:</i></b> The intravenous administration of HGF after the onset of renal dysfunction exerted a pharmacological effect on AKI, and renal injury did not affect the clearance of plasma HGF. This unaffected profile may serve as a base for the safety of HGF during therapeutic administration.

**背景与目的：** 肝细胞生长因子（Hepatocyte growth factor, HGF）可参与肾脏的再生与保护过程，但目前关于HGF治疗性给药的药代动力学相关研究数据仍较为匮乏。本研究中，研究人员在肾脏损伤发生后给予HGF，并在有效给药剂量下同步开展药代动力学分析。
**方法：** 针对药效学研究，研究人员向甘油诱导型急性肾损伤（AKI）模型大鼠静脉给予重组人HGF；在药代动力学研究中，分别采用甘油注射或肾脏缺血再灌注造模的大鼠作为AKI模型，采用5/6肾切除术造模的大鼠作为慢性肾病（CKD）模型。
**结果：** 当以0.5~2.0 mg/kg的剂量静脉给予HGF后，大鼠血尿素氮水平升高的情况得到抑制，表明HGF发挥了明确的药效学作用。但在正常对照组、AKI模型组与CKD模型组之间，清除率、分布容积、半衰期等药代动力学参数均未出现显著差异。
**结论：** 肾脏功能损伤发生后静脉给予HGF可对AKI产生药理学治疗作用，且肾脏损伤并不会影响血浆HGF的清除过程。这一不受疾病状态影响的药代动力学特征，可为HGF治疗给药的安全性提供理论依据。