Altered Brain Penetration of Diclofenac and Mefenamic Acid, but Not Acetaminophen, in Shiga-Like Toxin II-Treated Mice
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概要
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It is well accepted that bacterial and virus infections elevate the levels of cytokines in serum and cerebrospinal fluids. Such high levels of cytokines might alter the integrity of the blood-brain barrier (BBB) and/or blood-cerebrospinal fluid barrier (BCSFB), subsequently affecting brain penetration of drugs. However, few reports have addressed this issue. Thus, we investigated brain penetration of cyclooxygenase (COX) inhibitors, commonly used as antipyretics, in mice treated with Shiga-like toxin II (SLT-II) derived from E. coli O157:H7, which significantly elevates cytokine levels. As antipyretics, we used diclofenac, mefenamic acid, and acetaminophen. We found that SLT-II significantly increased the brain-to-plasma concentration ratio (Kp) of diclofenac and mefenamic acid, but not of acetaminophen. Moreover, the Kp of diclofenac and mefenamic acid was increased by probenecid, an anionic compound. These results suggest that efflux anion transporters might be involved in the transport of diclofenac and mefenamic acid. Western blot analysis revealed that SLT-II decreased the expression of organic anion transporter-3, an efflux transporter located on the BBB and/or BCSFB. Taken together, these results suggest that SLT-II and/or SLT-II-stimulated cytokines might change brain penetration of drugs and could possibly increase the risk of their side-effects by altering the expression of transporters.
- 社団法人 日本薬理学会の論文
- 2005-04-20
著者
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Fukuda Masaya
Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medica
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Takagi K
Department Of Medical Technology Nagoya University School Of Health Sciences
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MORISHIMA TSUNEO
Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutic
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Kubo Tatsuhiko
札幌医科大学 医学部公衆衛生学
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Kondo Takaaki
Department Of Internal Medicine Division Of Cardio-vascular Medicine
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TAKAGI Kenji
Department of Medical Technology, Nagoya University School of Health Sciences
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TAKAGI Kenzo
Department of Medical Technology, Nagoya University School of Health Sciences
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ABE Fumie
Department of Pharmacy and Pharmacokinetics, Aichi Medical University School of Medicine
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HASEGAWA Takaaki
Department of Pharmacy and Pharmacokinetics, Aichi Medical University School of Medicine
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KITAICHI Kiyoyuki
Department of Medical Technology, Nagoya University School of Health Sciences
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FUJIMOTO Yohei
Department of Medical Technology, Nagoya University School of Health Sciences
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Takagi Kenzo
Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un
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Fukuda Masaya
Department Of Cardiovascular Medicine Graduate School Of Medical Sciences Kumamoto University
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Fukuda Masaya
Department Of Medical Technology Nagoya University School Of Health Sciences
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Abe Fumie
Department Of Pharmacy And Pharmacokinetics Aichi Medical University School Of Medicine
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Abe Fumie
Department Of Mechanical Engineering Faculty Of Engineering Science Osaka University
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Hasegawa Takaaki
Department Of Pharmacy And Pharmacokinetics Aichi Medical University School Of Medicine
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Hasegawa Takaaki
Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un
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Takagi Kenzo
Department Of Internal Medicine Nagoya University School Of Medicine
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Fujimoto Yohei
Department Of Aeronautics And Astronautics Kyushu University
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Takagi Kenzo
Department Of Medical Technology Nagoya University School Of Health Sciences
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Kondo Takaaki
Department Of Medical Technology Nagoya University School Of Health Science
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Kitaichi Kiyoyuki
Department Of Cardiology Nagoya University Graduate School Of Medicine
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Hasegawa Takaaki
Department Of Hospital Pharmacy Nagoya University School Of Medicine
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Morishima Tsuneo
Department Of Pediatrics Okayama University School Of Medicine
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Morishima Tsuneo
Department Of Health Science Nagoya University
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Takagi Kenji
Department Of Cardiology Nagoya University Graduate School Of Medicine
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HASEGAWA Takaaki
Department of Bacteriology, Nagoya University School of Medicine
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