title: The apical uptake transporter of levofloxacin is distinct from the peptide transporter in human intestinal epithelial Caco-2 cells.
abstract: The aim of this study was to investigate the involvement of the peptide transporter for absorption of levofloxacin in Caco-2 cells. To evaluate the activity of apical and basolateral peptide transport, we first performed pharmacokinetic analysis of transcellular transport of glycylsarcosine (Gly-Sar) in cell monolayers grown on porous membrane filters. Transcellular transport of Gly-Sar at the medium pH 6 was greater in the apical-to-basolateral direction than in the opposite direction. Influx clearance of Gly-Sar at the apical membrane was much greater than basolateral influx and efflux clearance, indicating that the apical peptide transporter plays an important role in directional transcellular transport of the dipeptide across Caco-2 cell monolayers. We then evaluated the effect of various compounds on the uptake of Gly-Sar and levofloxacin at the apical membrane of Caco-2 cells. The apical uptake of [3H]Gly-Sar was significantly inhibited by Ala-Ala, Gly-Sar, and also levofloxacin, whereas that of [14C]levofloxacin was not inhibited by Ala-Ala and Gly-Sar. On the other hand, the apical uptake of [14C]levofloxacin was inhibited by nicotine, enalapril, fexofenadine, and L-carnitine. These findings indicated that the apical uptake transporter of levofloxacin is distinct from the peptide transporter in Caco-2 cells.
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Fukumori
authors.forename: Toshiya
authors.initials: T
authors.lastname: Murata
authors.forename: Mari
authors.initials: M
authors.lastname: Takaai
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Tahara
authors.forename: Masato
authors.initials: M
authors.lastname: Taguchi
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002451:Cell Compartmentation; D004151:Dipeptides / Q000493:pharmacokinetics* / Q000494:pharmacology; D024841:Fluoroquinolones / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D064704:Levofloxacin; D026901:Membrane Transport Proteins / Q000502:physiology; D015242:Ofloxacin / Q000378:metabolism* / Q000494:pharmacology; D000074011:Peptide Transporter 1; D027981:Symporters / Q000502:physiology*
chemical_list: D004151:Dipeptides; D024841:Fluoroquinolones; D026901:Membrane Transport Proteins; D000074011:Peptide Transporter 1; C082186:SLC15A1 protein, human; D027981:Symporters; C067802:intestinal peptide-proton cotransporter; C004194:glycylsarcosine; D064704:Levofloxacin; D015242:Ofloxacin; C053091:lomefloxacin