Screening of Antibiotics That Interact with Organic Anion-Transporting Polypeptides 1B1 and 1B3 Using Fluorescent Probes

Access this Article

Author(s)

    • Yamaguchi Hiroaki Yamaguchi Hiroaki
    • Department of Pharmaceutical Sciences, Tohoku University Hospital|Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University
    • Takeuchi Toshiko Mano Nariyasu
    • Department of Pharmaceutical Sciences, Tohoku University Hospital|Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University
    • Okada Masahiro
    • Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University
    • Kobayashi Minako
    • Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University
    • Unno Michiaki
    • Division of Gastroenterological Surgery, Department of Surgery, Tohoku University Graduate School of Medicine
    • Abe Takaaki
    • Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Biomedical Engineering
    • Goto Junichi
    • Department of Pharmaceutical Sciences, Tohoku University Hospital
    • Hishinuma Takanori
    • Division of Pharmacotherapy, Graduate School of Pharmaceutical Sciences, Tohoku University
    • Shimada Miki
    • Department of Pharmaceutical Sciences, Tohoku University Hospital|Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University

Abstract

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.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 34(3), 389-395, 2011

    Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130000657818
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    0918-6158
  • NDL Article ID
    10990080
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-V41
  • Data Source
    NDL  IR  J-STAGE 
Page Top