| Project/Area Number |
23590177
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MIYAMOTO Ken-ichi 金沢大学, 附属病院, 教授 (30100514)
WADA Takashi 金沢大学, 医学系, 教授 (40334784)
TERAMACHI Hitomi 岐阜薬科大学, 薬学部, 教授 (20405129)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | がん / バンコマイシン / 腎クリアランス / 亢進 / サイトカイン / 骨肉腫 / vancomycin / 蛋白結合率 / セファゾリン / 酸化ストレス |
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| Research Abstract |
Recently, it has been reported that vancomycin (VCM) total clearance (CLtot) is significantly higher in patients with malignancies compared to those without malignancies. In the present study, to clarify the mechanism of VCM CLtot enhancement in malignancy, we adopted the population pharmacokinetic analysis and the rat animal models, using chemical carcinogen-induced osteosarcoma, transplanted into thigh muscles. The CLtot and renal clearance (CLr) of VCM in the tumor-bearing rats were increased compared to that of the control rats. However, there was no difference in the glomerular filtration rate. The plasma concentrations of cytokines, were elevated in tumor-bearing rats. When cytokines were simultaneously exposed to renal proximal tubular epithelial (RPTEC) cells, VCM secretory ratio increased significantly. These findings suggest that the change in VCM tubular secretion or reabsorption by cytokines might be associated with the VCM CLtot enhancement in the tumor-bearing rats.
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