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Screening of antibiotics that interact with organic anion-transporting polypeptides 1B1 and 1B3 using fluorescent probes.

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Title: Screening of antibiotics that interact with organic anion-transporting polypeptides 1B1 and 1B3 using fluorescent probes.
Authors: Yamaguchi, Hiroaki Browse this author →KAKEN DB
Takeuchi, Toshiko Browse this author
Okada, Masahiro Browse this author
Kobayashi, Minako Browse this author
Unno, Michiaki Browse this author
Abe, Takaaki Browse this author
Goto, Junichi Browse this author
Hishinuma, Takanori Browse this author
Shimada, Miki Browse this author
Mano, Nariyasu Browse this author
Keywords: antibiotic
interaction
screening
organic anion-transporting polypeptide 1B1
organic anion-transporting polypeptide 1B3
Issue Date: Mar-2011
Publisher: Pharmaceutical Society of Japan
Journal Title: Biological & pharmaceutical bulletin
Volume: 34
Issue: 3
Start Page: 389
End Page: 395
Publisher DOI: 10.1248/bpb.34.389
PMID: 21372390
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.
Type: article
URI: http://hdl.handle.net/2115/50390
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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