| Project/Area Number |
13307068
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | KYOTO UNIVERSTTY |
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Principal Investigator |
INUI Ken-ichi Kyoto University, Pharmacy, Professor, 医学研究科, 教授 (70034030)
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| Co-Investigator(Kenkyū-buntansha) |
MASUDA Satohiro Kyoto University, Pharmacy, Instructor, 医学研究科, 助手 (90303825)
KATSURA Toshiya Kyoto University, Pharmacy, Lecturer, 医学研究科, 講師 (10283615)
OKUDA Masahiro Kyoto University, Pharmacy, Associate Professor, 医学研究科, 助教授 (70252426)
TERADA Tomohiro Kyoto University, Pharmacy, Instructor, 医学研究科, 助手 (10324641)
MOTOHASHI Hideyuki Kyoto University, Pharmacy, Instructor, 医学研究科, 助手 (30359822)
矢野 育子 京都大学, 医学研究科, 助手 (50273446)
齋藤 秀之 京都大学, 医学研究科, 助教授 (40225727)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥48,360,000 (Direct Cost: ¥37,200,000、Indirect Cost: ¥11,160,000)
Fiscal Year 2003: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2002: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Fiscal Year 2001: ¥26,780,000 (Direct Cost: ¥20,600,000、Indirect Cost: ¥6,180,000)
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| Keywords | Drug transporter / Personalized pharmacotherapy / Interindividual differences / Genetic polymorphism / Expression profile / Detoxification system / Renal excretion / Organic ion / 尿細管分泌 / オーダーメイド薬物療法 / アニオン性薬物 / カチオン性薬物 / ペプチド類似薬物 / 有機カチオン / 有機アニオン / 腎疾患 / 薬物相互作用 / 薬物動態 / 遺伝子発現 |
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| Research Abstract |
Drug transporters expressed in the kidney play important roles for elimination of number of hydrophilic compounds such as drugs, toxins and endogenous compounds. In the present study, we evaluated interindividual differences of pharmacokinetic (PK) properties based on the genetic information and expression profiles of human renal drug transporters.
We have identified and characterized novel renal specific transporters hOCT2-A and NaGLT1. Expression profiles for various drug transporters such as organic ion transporters in the human kidney were constructed. We have identified single nucleotide polymorphisms for coding region (cSNPs) of hOCT1 and hPEPT2 with decreasing the functional activities, but the appearance rates of these SNPs were very low. The correlation analyses between expression of drug transporters and PK properties in renal failure patients and model animals indicated that expression levels of renal drug transporters are responsible for interindividual differences of drug renal excretion. These findings could provide information for quantitative prediction and evaluation of PK based on the expression levels of renal drug transporters.
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