2013 Fiscal Year Final Research Report
Regulation of functions of drug transporters in renal tubules by inflammatory cytokines and implication of its significance
| Project/Area Number |
23590180
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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 | Mie University |
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Principal Investigator |
OKUDA Masahiro 三重大学, 医学部附属病院, 教授 (70252426)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMOTO Takuya 三重大学, 医学部附属病院, 准教授 (30447867)
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| Project Period (FY) |
2011 – 2013
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| Keywords | メトトレキサート / リポ多糖 / ラット / 有機アニオントランスポータ / 腎クリアランス |
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| Research Abstract |
Plasma clearance of methotrexate (MTX) decreased about 50% in the inflammatory rat model, which is prepared by the administration of lipopolysaccharide (LPS). Involvement of glomerular filtration as well as tubular secretion were suggested in the decreased renal clearance of MTX by LPS. Renal tissue/plasma concentration ratio and efflux clearance from renal tissue to the tubular lumen also decreased in LPS rats, and were comparable to the decreased expression levels of organic anion transporters (rOAT1, rOAT3, rMRP2, rMRP4) in the kidney. In conclusion, the renal clearance of MTX markedly decreased in the LPS-treated rats and the contribution of decreased glomerular filtration as well as decreased expression levels of organic anion transporters in the renal tubules were suggested.
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