2017 Fiscal Year Final Research Report
Drug resistance caused by intracellular pharmacokinetics
| Project/Area Number |
15K08066
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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 | Gunma University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
荒木 拓也 群馬大学, 大学院医学系研究科, 准教授 (00568248)
坡下 真大 名古屋市立大学, 大学院薬学研究科, 講師 (20613384)
永野 大輔 群馬大学, 大学院医学系研究科, 助教 (90738387)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 薬剤抵抗性 / 薬動力学 / 細胞内薬物濃度 |
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| Outline of Final Research Achievements |
To establish a method of dosage adjustment for darunavir (DRV) based on pharmacokinetic theory, we analyzed the correlation between DRV levels in peripheral blood mononuclear cells (PBMCs) and plasma. An in vitro kinetic study using MOLT-4 cells was performed to assess the contribution of RTV to the intracellular accumulation of DRV. We found a poor correlation between intracellular DRV and plasma DRV levels in patients receiving HAART. The efflux rate of DRV from cells was slow; therefore, the concentration of DRV in PBMCs may reflect average exposure to the drug and clinical efficacy.
The contribution of carrier-mediated transport systems on the biliary elimination of gadoxetate was examined. The geometrical isomer with specific conformation corresponding to 22.6% of gadoxetate was eliminated into bile in rats via a carrier-mediated transport system no later than 30min after intravenous injection.
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| Free Research Field |
臨床薬理学
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