Characteristics of uptake of neutral and anionic cephalosporin antibiotics by the cloned intestinal peptide transporter PePT1

U. Wenzel, I. Gebert, H. Daniel

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Uptake of the orally active cephalosporin antibiotics into intestinal epithelial cells is mediated by the H+-coupled electrogenic peptide transport system PepTL Since studies in humans show that anionic cephalosporms have a considerably lower bioavailability than the neutral aminocephalosporins, we compared the characteristics of uptake of a neutral (3H-cefadroxil) and an anionic compound (14C-cefixime) into Xenopus laavis oocytes expressing the rabbit intestinal peptide transporter PepT1. Influx of H+-ions as a consequence of cephalosporin transport was determined by changes in pHin in oocytes measured by dual emission fluorometry based on the pH-dependent fluorescence changes of the dextran-coupled dye SNARF-1. A conventional two-electrode voltage clamp technique was applied to characterize responses in current and transmembrane potential to β-lactam transport. Results: Influx of both cephalosporins displayed a pronounced pH dependence with a pH optimum of 5.0 for cefixime and pH 6.5 for cefadroxii. Under these conditions cefixime and cefadroxil were transported with similar Km and Vmax values. Cross-inhibition in uptake of cefadroxil and cefixime was obtained only at pH < 5.5 indicating that anionic compounds do not interact with Peptl at pH > 6.5. Single cell pHin recordings and electrophysiology established that both compounds are transported by PepT1 by electrogenic H+ coupled cotransport at pH 5.5 (cefixime) and pH 6.5 (cefadroxil) but with different flux coupling ratios. Although both compounds use the same transporter for absorption, cefixime needs a lower intestinal pH for maximal absorption that may not be realized in vivo due to an only slightly acidic mucosal surface pH in the small intestine.

Original languageEnglish
Pages (from-to)A283
JournalFASEB Journal
Issue number3
StatePublished - 1996
Externally publishedYes


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