| Project/Area Number |
16K08416
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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 | Tokyo University of Science |
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Principal Investigator |
Aoyama Takao 東京理科大学, 薬学部薬学科, 教授 (60262028)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肺MAC症 / クラリスロマイシン / リファンピシン / レボフロキサシン / キノロン系抗菌薬 / 薬物相互作用 / MDR1 / 気道上皮被覆液 / CYP3A / クロリスロマイシン / フルオロキノロン / トランポーター |
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| Outline of Final Research Achievements |
We reported that the combination therapy of levofloxacin (LVFX) and recommended regimen, which includes clarithromycin (CAM) and rifampicin (RFP) aggravated clinical outcome of pulmonary Mycobacterium avium complex (MAC) disease. We considered that the pharmacokinetic interaction that lowering the concentration of CAM at the therapeutic target site (epithelial lining fluid; ELF) was the cause of poor clinical outcome, we investigated the pharmacokinetic interaction between CAM and LVFX in RFP pretreated mice. CYP3A expression level was increased in liver and small intestine, and MDR1 also increased in lung, but there were no significant differences in the concentrations of CAM in ELF between CAM;LVFX group (20;150, 40;100, 60;50 mg/kg p.o.) and CAM group. However, the transfer rate of CAM to ELF decreased with increasing doses of LVFX. Our results suggested that taking CAM, LVFX and RFP in combination may cause aggravation of the clinical outcome of MAC disease.
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| Academic Significance and Societal Importance of the Research Achievements |
近年増加傾向にあるMycobacterium aviumを原因菌とする肺MAC症の治療は主薬のクラリスロマイン（CAM）にリファンピシン（RFP）などを併用する。治療に難渋する場合にはレボフロキサシン（LVFX）等のキノロン系抗菌薬が併用するが、反対に効果が減弱することがある。そこで、肺MAC症患者を想定したRFP前処置マウスにCAMおよびLVFXを経口投与後のCAMの体内動態を検討した結果、LVFX併用により肺組織から治療標的部位の気道上皮被覆液（ELF）へのCAM移行率が低下する傾向が見られた。患者においても同様の現象が起きている可能性があり、治療において留意すべきであると考える。
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