Pharmacokinetics and Pharmacodynamics of Mycophenolic Acid and Individualized Therapy
Project/Area Number |
25460210
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Medical pharmacy
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Research Institution | Kyoto University |
Principal Investigator |
Yano Ikuko 京都大学, 薬学研究科(研究院), 准教授 (50273446)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | 免疫抑制薬 / 母集団解析 / M & S / 造血幹細胞移植 / ミコフェノール酸 / IMPDH / M&S / ポピュレーション解析 / PK/PD解析 / TDM / NAR / 免疫抑制剤 |
Outline of Final Research Achievements |
The experimental data obtained from Nagase analbuminemic rats showed that the free mycophenolic acid (MPA) concentration was suitable for the biomarker of immunosuppressive effect of MPA. Simulations based on the obtained pharmacokinetic and pharmacodynamic parameters showed that the pharmacological marker IMPDH activity decreased non-linearly according to the increase in free fraction of MPA, although the area under the concentration-time curve of free MPA increased linearly.Population pharmacokinetic and pharmacodynamic analyses using clinical data obtained from hematopoietic stem cell transplant patients showed that the decreased renal failure increased the MPA concentration by the increased enterohepatic circulation of the accumulated metabolite, but scarcely affected the pharmacological effects. In conclusion, since the pharmacodynamics of MPA was non-linear, the increased MPA concentration has a limited effect on the pharmacological effects of MPA.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Pharmacokinetics and pharmacodynamics of mycophenolic acid in Nagase analbuminemic rats: Evaluation of protein binding effects using the modeling and simulation approach.2015
Author(s)
Yoshimura, K., Yano, I., Kawanishi, M., Nakagawa, S., Yonezawa, A., Matsubara, K.
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Journal Title
Drug Metab. Pharmacokinet.
Volume: 30
Issue: 6
Pages: 441-448
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Sensitive and validated LC-MS/MS methods to evaluate mycophenolic acid pharmacokinetics and pharmacodynamics in hematopoietic stem cell transplant patients.2015
Author(s)
Kawanishi, M., Yano, I., Yoshimura, K., Yamamoto, T., Hashi, S., Masuda, S., Kondo, T., Takaori-Kondo, A., Matsubara, K.
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Journal Title
Biomed. Chromatogr.
Volume: 印刷中
Issue: 9
Pages: 1309-1316
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Monitoring mycophenolate mofetil is necessary for the effective prophylaxis of acute graft versus host disease after cord blood transplantation.2015
Author(s)
Arai, Y., Kondo, T., Kitano, T., Hishizawa, M., Yamashita, K., Kadowaki, N., Yamamoto, T., Yano, I., Matsubara, K., Takaori-Kondo, A.
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Journal Title
Bone Barrow Transplant.
Volume: 50
Issue: 2
Pages: 312-314
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Assessment of four methodologies (MEIA, CLIA, ACMIA, and FIA-MS/MS) for measuring tacrolimus blood concentration in Japanese liver transplant patients.2014
Author(s)
Hashi S, Masuda S, Kikuchi M, Uesugi M. Yano I, Omura T, Yonezawa A, Fujimoto Y, Ogawa K, Kaido T, Uemoto S, Matsubara K
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Journal Title
Transplant Proc.
Volume: 未定
Related Report
Peer Reviewed
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[Journal Article] 非小細胞肺がん患者に対する簡易懸濁法を用いたエルロチニブ投与に関する検討2013
Author(s)
髙田哲也, 池見泰明, 福土将秀, 杉本充弘, 石橋直哉, 小林政彦, 矢野育子, 金 永学, 三嶋理晃, 芦原英司, 松原和夫
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Journal Title
医療薬学
Volume: 39
Pages: 565-570
Related Report
Peer Reviewed
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