Screening of Antibiotics That Interact with Organic Anion-Transporting Polypeptides 1B1 and 1B3 Using Fluorescent Probes
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概要
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Hepatic organic anion transporters OATP1B1 and OATP1B3 are expressed at the sinusoidal membrane of hepatocytes and contribute to the hepatic uptake of a wide variety of clinically used drugs. To identify the antibiotics that interact with the human organic anion transporters OATP1B1 and OATP1B3, we applied a screening system using fluorescent probes. Twenty-six antibiotics with a variety of mechanisms of action were examined. The screening demonstrated that four antibiotics inhibited OATP1B1-mediated transport and 11 antibiotics inhibited OATP1B3-mediated transport in a concentration-dependent manner. Antibiotics that inhibited OATP1B3-mediated transport tended to exhibit higher affinity than those that inhibited OATP1B1-mediated transport. To clarify whether the antibiotics that interacted with OATP1B1 and/or OATP1B3 were substrates for these transporters, an uptake study was performed. Rifampicin and penicillin were transported by both OATP1B1 and OATP1B3. Moreover, OATP1B3 was involved in the transport of ceftriaxone, cefmetazole, cefoperazone, and cefotaxime. Macrolides were not significantly transported by either transporter. In conclusion, the results demonstrated that our system is a useful method for the rapid screening of transporter–antibiotic interaction, and we found novel substrates. Our results indicate that OATP1B1 and/or OATP1B3 contribute to the transport process of some antibiotics, and that drug–drug interactions associated with these transporters could occur after the administration of antibiotics.
著者
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YAMAGUCHI Hiroaki
Department of Electronics, Nagoya University
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MANO Nariyasu
Department of Pharmacy, Tohoku University Hospital
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Mano N
Tsukuba Research Laboratories Eisai Co. Ltd.
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Shimada Miki
Department of Pharmaceutical Sciences, Tohoku University Hospital
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ABE TAKAAKI
Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku Univers
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HISHINUMA TAKANORI
Division of Pharmacotherapy, Graduate School of Pharmaceutical Sciences, Tohoku University
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Goto Junichi
Department Of Surgery Asahikawa Medical College
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Goto J
The Ion Engineering Research Institute Corporation
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UNNO Michiaki
Division of Gastroenterological Surgery, Endocrinology and Vascular Medicine, Tohoku University Grad
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Yamaguchi Hiroaki
Department Of Cardiolgy Tokyo Metropolitan Hiroo General Hospital
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Unno Michiaki
Division Of Biological Regulation And Oncology Department Of Surgery Tohoku University Graduate Scho
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Goto J
Division Of Clinical Pharmacy Graduate School Of Pharmaceutical Sciences Tohoku University
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Okada Masahiro
Division Of Cardiovascular Surgery National Hospital Organization Okayama Medical Center
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Mano Nariyasu
Analytical Chemistry And Pharmaceutical Research Section Tsukuba Research Laboratories Eisai Co. Ltd
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Abe Takaaki
Division Of Nephrology Endocrinology And Vascular Medicine Department Of Medicine Tohoku University
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Hishinuma Takanori
Division Of Pharmacotherapy Graduate School Of Pharmaceutical Sciences Tohoku University
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Shimada Miki
Department Of Clinical Pharmacy Tohoku University Graduate School Of Pharmaceutical Sciences
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Mano Nariyasu
Department Of Clinical Pharmacy Tohoku University Graduate School Of Pharmaceutical Sciences
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Shimada Miki
Dep. Of Pharmaceutical Sciences Tohoku Univ. Hospital
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Aoki Takeshi
Division Of Nephrology Endocrinology And Vascular Medicine Tohoku University Graduate School Of Medi
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Takeuchi Toshiko
Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University
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Kobayashi Minako
Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University
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Hishinuma T
Division Of Clinical Pharmacy Graduate School Of Pharmaceutical Sciences Tohoku University
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Goto Junichi
Department Of Pharmaceutical Sciences Tohoku University Hospital
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Unno Michiaki
Division of Gastroenterological Surgery, Department of Surgery, Tohoku University Graduate School of Medicine
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Mano Nariyasu
Department of Pharmaceutical Sciences, Tohoku University Hospital
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Abe Takaaki
Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Biomedical Engineering
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Abe Takaaki
Division of Medical Science, Tohoku University Graduate School of Biomedical Engineering
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