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• W2158822910 abstract "Some cephalosporins, such as cefadroxil, are orally available. H⁺-coupled peptide transporter 1 mediates the transport of cephalosporins across the apical membrane of enterocytes. It is not known which mechanism(s) is responsible for the subsequent transport of cephalosporins across the basolateral membrane toward the circulation. We have tested whether ATP-binding cassette (ABC) transporters ABCC3 and/or ABCC4 are involved in the latter process. Transport experiments with plasma membrane vesicles expressing these transporters were used to determine whether ABCC3 and ABCC4 can transport cephalosporins in vitro. The involvement of Abcc3 and Abcc4 in the transport of cefadroxil from enterocytes was subsequently studied using intestinal explants from wild-type, <i>Abcc3</i>(−/−), <i>Abcc4</i>(−/−), and <i>Abcc3</i>(−/−)/<i>Abcc4</i>(−/−) mice in an Ussing chamber setup. Finally, appearance of cefadroxil in portal blood was investigated in vivo after intrajejunal administration of cefadroxil in wild-type, <i>Abcc3</i>(−/−), <i>Abcc4</i>(−/−), and <i>Abcc3</i>(−/−)<i>/Abcc4</i>(−/−) mice. ABCC3- and ABCC4-mediated transport of estradiol-17β-glucuronide was dose-dependently inhibited by cephalosporins in vesicular transport experiments. Furthermore, transport of cefadroxil by ABCC3 and ABCC4 was saturable with <i>K</i>_m values of 2.5 ± 0.7 and 0.25 ± 0.07 mM, respectively. Transport of cefadroxil from the apical to the basolateral side of jejunal tissue explants was unchanged in <i>Abcc3</i>(−/−) but significantly reduced (approximately 2-fold) in <i>Abcc4</i>(−/−) and <i>Abcc3</i>(−/−)/<i>Abcc4</i>(−/−) when compared with wild-type tissue. Upon instillation of cefadroxil in the jejunum, portal and peripheral blood concentrations were similar in <i>Abcc3</i>(−/−) and <i>Abcc4</i>(−/−) but approximately 2-fold reduced in <i>Abcc3</i>(−/−)/<i>Abcc4</i>(−/−) compared with wild-type mice. Our data demonstrate that intestinal absorption of cefadroxil depends partly on ABCC3 and ABCC4." @default.
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• W2158822910 date "2011-12-13" @default.
• W2158822910 modified "2023-10-09" @default.
• W2158822910 title "Oral Availability of Cefadroxil Depends on ABCC3 and ABCC4" @default.
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• W2158822910 doi "https://doi.org/10.1124/dmd.111.041731" @default.
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