| Project/Area Number |
24590210
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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 | Yokohama College of Pharmacy (2013-2014)
Keio University (2012) |
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Principal Investigator |
CHIBA Koji 横浜薬科大学, 薬学部, 教授 (30458864)
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| Co-Investigator(Kenkyū-buntansha) |
SUWA Toshio 慶應義塾大学, 薬学部, 教授 (20383664)
MATSUSHIMA Yukiko 慶應義塾大学, 薬学部, 講師 (10618531)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 民族差 / CYP2D6 / CYP２C19 / 個体間変動 / モンテカルロシミュレーション / ポピュレーションファーマコキネティクス / 薬物動態 / モデリング / シミュレーション / 母集団薬物動態解析 / 抗菌薬 / CYP2C19 / CYP2C9 / 遺伝子多型 / 低分子ヘパリン / 腎クリアランス |
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| Outline of Final Research Achievements |
In this study, Monte Carlo simulation were conducted using population pharmacokinetic (PPK) models for 22 antibiotics which were constructed for mainly Caucasians with adjustment of covariate to Japanese. Reported Japanese Cmax and AUC were compared with simulated values. The results suggested that almost all PPK models for Caucasian were applicable for prediction of Japanese exposure except for some models of cephems, glycopeptides and aminoglycosides presumably due to inappropriate inter-individual variability (IIV) in the models. To determine absorption process after subcutaneous injection of protein drugs, new PPK models for dalteparin were constructed. Ethnic differences between Caucasian and Japanese were accounted for by body weight. Variability of intrinsic clearance reflected by IIV of enzyme activity was estimated for CYP2D6 and CYP2C9. By using the variability, ethnic differences of variability of AUC were successfully predicted.
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