Tanaka H, Tokiwa T
Pharmaceutical Development Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Cancer Res. 1990 Oct 15;50(20):6615-9.
The pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was studied in rats experiencing renal and hepatic failure. The serum concentration of rhG-CSF after i.v. administration to male Sprague-Dawley rats at a dose of 10 micrograms/kg was investigated by a sandwich enzyme immunoassay. Total-body clearance of rhG-CSF was 44.48 ml/h/kg in sham-operated rats compared with 9.429 ml/h/kg in bilaterally nephrectomized rats. In sham-operated rats, the half-life (beta) of rhG-CSF was 1.512 h, and it increased to 5.333 h after nephrectomy. The volumes of distribution were identical in both rats. In rats with acute renal failure induced by uranyl nitrate, the clearance and volume of distribution were identical to those of control rats, but the half-life (beta) was slightly shorter. In partially (70%) hepatectomized rats, the clearance of rhG-CSF decreased from 42.08 ml/h/kg to 31.93 ml/h/kg. Similar half-lives were observed in rats in both the sham-operated and hepatectomized groups. However, the volume of distribution decreased after hepatectomy. In rats with hepatic failure induced by CCl4, the pharmacokinetic changes were similar to those observed in hepatectomized rats. These results suggest that renal clearance makes a major contribution to total-body clearance compared with hepatic clearance.
在肾衰竭和肝衰竭大鼠中研究了重组人粒细胞集落刺激因子（rhG-CSF）的药代动力学。通过夹心酶免疫测定法研究了以10微克/千克的剂量静脉注射给雄性Sprague-Dawley大鼠后rhG-CSF的血清浓度。假手术大鼠中rhG-CSF的全身清除率为44.48毫升/小时/千克，而双侧肾切除大鼠中为9.429毫升/小时/千克。在假手术大鼠中，rhG-CSF的半衰期（β）为1.512小时，肾切除后增加到5.333小时。两组大鼠的分布容积相同。在硝酸铀酰诱导的急性肾衰竭大鼠中，清除率和分布容积与对照大鼠相同，但半衰期（β）略短。在部分（70%）肝切除的大鼠中，rhG-CSF的清除率从42.08毫升/小时/千克降至31.93毫升/小时/千克。假手术组和肝切除组大鼠的半衰期相似。然而，肝切除后分布容积减小。在四氯化碳诱导的肝衰竭大鼠中，药代动力学变化与肝切除大鼠中观察到的相似。这些结果表明，与肝脏清除相比，肾脏清除对全身清除起主要作用。
