著者

天野 潤 平松 優佳 早川 直彦 加藤 基浩 岡野 健 木下 春喜 岡崎 彬

出版者

The Japanese Society for the Study of Xenobiotics

雑誌

薬物動態 (ISSN:09161139)

巻号頁・発行日

vol.8, no.6, pp.1199-1212, 1993-12-30 (Released:2007-03-29)

参考文献数

31

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The metabolites of rG·CSF present in the serum were investigated in rats after intravenous administration of 125I-rG·CSF at the dose of 10μg/kg, or nonlabeled-rG·CSF at the dose of 100-400μg/kg. 1. Using gel filtration on the Superose 12 column, most of the radioactivity in rat serum at 30min after administration of 125I-rG·CSF was eluted at a point corresponding to molecular weight of 19kd, this point was the same as that of intact-rG·CSF. The radioactivity was immunoreactive with anti-rG·CSF antibody and showed biological activity against NFS-60 cell lines. At 2 and 6h after administration, the radioactivity present in the serum was eluted from the column at a point corresponding to molecular weight of 46kd and 19kd. The radioactivity corresponding to 46kd showed immunoreactivity, but was biologically inactive. 2. The SDS-polyacrylamide gel electrophoresis revealed that most of the radioactivity in the serum present at 30min after administration of 125I-rG·CSF was detected at a point corresponding to intact-rG·CSF (molecular weight of 19kd). The radioactivity was also detected at a point corresponding to molecular weight of 19kd and 5kd at 2h, 19kd, 14kd and 5kd at 6h after administration. 3. The chromatofocusing using Mono-P column showed that most of the radioactivity in the serum was focused at a point corresponding to isoelectric points of 5.8 and 5.5 at 30min after administration of 125I-rG·CSF, these points were related to monosialo-rG·CSF and disialo-rG· CSF, respectively. At 2 and 6h after administration, the radioactivity showing immunoreactivity was newly found at a point corresponding to isoelectric points of 5.2 and 4.5. 4. During immunoblotting of serum samples after administration of nonlabeled-rG·CSF, the presence of a band corresponding to molecular weight of 19kd was found in all sampling times after administration. Beside the band of 19kd, only bands at a point corresponding to molecular weight of 5kd and 14kd were detected at 6h after administration. 5. Based of the fact that only an intact form of rG·CSF exists at early stage after intrave nous administration of rG·CSF, and since 2h the metabolites which have not biological activity appeared in the serum, we have concluded that an intact form mainly participate in hematologic activity of rG·CSF in vivo.

著者

加藤 基浩 天野 潤 岡野 健 平松 優佳 木下 春喜 岡崎 彬

出版者

The Japanese Society for the Study of Xenobiotics

雑誌

薬物動態 (ISSN:09161139)

巻号頁・発行日

vol.8, no.6, pp.1213-1218, 1993-12-30 (Released:2007-03-29)

参考文献数

15

被引用文献数

3

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To evaluate the role of the kidney in the elimination of rG·CSF, the pharmackinetics of rG·CSF was studied in rats upon removal of one (1/2-nephrectomized rat) or of two kidneys (nephrectomized rat). Plasma concentrations of rG·CSF were measured by enzyme immunoassay method. 1. The elimination half lives of rG·CSF in nephrectomized and 1/2-nephrectomized rats, which were 4.85h and 1.llh respectively, were longer than those in sham operated rats given rG·CSF 10μg/kg intravenously. Total nephrectomy and 1/2-nephrectomy resulted in 70% and 30% reduction of total body clearance of rG·CSF in rats, respectively. 2. The result suggested that the kidney is the major elimination site of rG·CSF.