著者

天野 潤

出版者

九州大学

巻号頁・発行日

2010

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博士論文

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 丹羽 一与 天野 潤 早川 直彦 神山 博 大久保 一三 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.4, pp.481-492, 1993-09-10 (Released:2007-03-29)

参考文献数

17

被引用文献数

1

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We studied the absorption, distribution, excretion and metabolism of 125I-EPOCH after single subcutaneous administration to rats. 1. The levels of immunoreactive rad ioactivity reached the maximum at 8 to 12 hours after dosing and declined monoexponentially with a half-life ranging from 5.77 to 7.47 hours at the doses of 0.5, 1, 5 and 25μg/kg. The MRT of immunoreactive radioactivity after sc dosing ranged from 13.83 to 17.01 hours at any dose levels. F value (AUCsc/AUCiv), which ranged from 0.31 to 0.48, tend to increase in proportion to the administered dose. 2. Most of tissues showed the highest level of total radioactivity at 10 hour after dosing. The level of radioactivity in tissues were lower, than that of serum, except the thyroid gland whose level was the highest. They declined parallel with disappearence of the radioactivity in serum. The level of radioactivity in brain was extremely low. The elimination half-life of radioactivity from the injection site was calculated to be 9h and 1.97% of the dose still remained there at 48 hour. 3. Until 96h after sc administration of 125I-EPOCH at the dose of 1μg/kg, urinary excretions of total, the TCA-precipitable and the immunoreactive radioactivity were 75.89%, 0.35%, 0.05%, respectively. Fecal excretion of total radioactivity was 2.97%, until 96h after dosing. 4. Gel filtration of the plasma showed that the radioactivity of low molecular weight was iodo ion, and that related to radioactivity of high molecular weight appeared mainly as an unchanged 125I-EPOCH.

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.

著者

加藤 基浩 丹羽 一与 天野 潤 早川 直彦 神山 博 大久保 一三 岡崎 彬

出版者

日本薬物動態学会

雑誌

薬物動態 (ISSN:09161139)

巻号頁・発行日

vol.8, no.4, pp.493-503, 1993

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We studied the absorption, distribution and excretion of radioactivity after 4 times multiple subcutaneous administrations of <SUP>125</SUP>I-EPOCH at an interval of 48 hours.<BR> 1. Plasma levels of immunoreactive radioactivity at 10h and 48h following each multiple administration did not change during the experimental period. There were no pronounced differences in pharmacokinetics between first and fourth administration.<BR> 2. The levels of radioactivity in spleen and bone marrow after multiple administration were slightly higher than those after administration of a single dose. Those in other tissues except thyroid gland, were similar to those after administration of a single dose. The remained radioactivity in the injection site at 10h after multiple administration was 33.65%, which was similar to that of single administration.<BR> 3. Until 96h after final administration of <SUP>125</SUP>I-EPOCH, urinary excretions of total. the TCA-precipitable and the immunoreactive radioactivity were 76.43%, 0.97%, 0.49%, respectively. Fecal excretion of total radioactivity was 3.83%, until 96h after final administration.

著者

天野 潤 伊川 由利子 塩川 理絵 奥谷 太一 宮山 崇 名波 雅彦 麻生 良典

出版者

日本薬物動態学会

雑誌

日本薬物動態学会年会講演要旨集

巻号頁・発行日

vol.23, pp.195, 2008

著者

中村 元気 天野 潤 金子 晃久 吉野 梓 中野 康之亮 石谷 雅樹

出版者

一般社団法人 日本薬物動態学会

雑誌

日本薬物動態学会年会講演要旨集 第25回日本薬物動態学会年会

巻号頁・発行日

pp.184, 2010 (Released:2010-12-15)