Pharmacokinetic study of recombinant human hepatocyte growth factor administered in a bolus intravenously or via portal vein
Pharmacokinetic study of recombinant human hepatocyte growth factor administered in a bolus intravenously or via portal vein
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DOI：
10.1016/j.hepres.2004.09.002
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发表时间：
2004-11-01
影响因子：
4.2
通讯作者：
Tsubouchi, H
中科院分区：
文献类型：
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作者：
Ido, A;Moriuchi, A;Tsubouchi, H
肝细胞生长因子(HGF)刺激肝脏再生，有可能成为治疗包括暴发性肝功能衰竭和肝硬变在内的致命肝病的药物。在这项研究中，我们研究了重组人肝细胞生长因子的药代动力学，它将很快进入临床应用。给正常大鼠静脉注射重组人HGF(0.1 mg/kg)，5min后血清HGF水平升高至89.7+/-20.6 ng/ml，半衰期为2.4min。静脉注射重组HGF主要分布于肝脏，并诱导肝组织c-Met酪氨酸磷酸化。相比之下，通过门静脉注射重组人HGF的大鼠血清HGF水平较低，肝脏分布较多。此外，与正常大鼠相比，70%肝部分切除或肝硬变大鼠的血清HGF水平升高，半衰期延长。这些结果表明，尽管半衰期短，但重组人HGF团注对致死性肝病患者仍有疗效，应根据肝损伤的程度调整剂量。(C)2004爱思唯尔B.V.保留所有权利。
Hepatocyte growth factor (HGF) stimulates liver regeneration and has the potential to be a therapeutic agent for fatal liver diseases, including fulminant hepatic failure and liver cirrhosis. In this study, we investigated the pharmacokinetics of recombinant human HGF, which will be soon available for clinical applications. When recombinant human HGF (0.1 mg/kg) was administered intravenously to normal rats, serum levels of human HGF increased to 89.7 +/- 20.6 ng/ml 5 min after the bolus injection, followed by a decrease with a half-life of 2.4 min. Recombinant HGF administered intravenously was distributed primarily to the liver and induced c-Met tyrosine phosphorylation in liver tissues. In comparison, rats given recombinant human HGF via the portal vein exhibited lower serum HGF and an increase in hepatic distribution. Additionally, when compared with normal rats, those with 70% partial hepatectomy or liver cirrhosis showed an increase in serum levels of human HGF with a prolonged half-life. These results suggest that, despite a short half-life, bolus injection of recombinant human HGF may induce therapeutic effect in patients with fatal live disease, and that the dose of this recombinant protein should be modulated according to the degree of liver injury. (C) 2004 Elsevier B.V. All rights reserved.