The apical uptake transporter of levofloxacin is distinct from the peptide transporter in human intestinal epithelial Caco-2 cells
| Autor: | Shiro Fukumori, Katsutoshi Tahara, Masato Taguchi, Toshiya Murata, Yukiya Hashimoto, Mari Takaai |
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| Rok vydání: | 2008 |
| Předmět: |
Ofloxacin
animal structures Pharmaceutical Science Levofloxacin Pharmacology Peptide Transporter 1 Intestinal absorption Humans Pharmacology (medical) skin and connective tissue diseases integumentary system biology Symporters Membrane transport protein Chemistry fungi Membrane Transport Proteins Transporter Biological Transport Dipeptides Apical membrane Cell Compartmentation body regions Intestinal Absorption Peptide transport Caco-2 Paracellular transport Symporter biology.protein Biophysics Caco-2 Cells Fluoroquinolones |
| Zdroj: | Drug metabolism and pharmacokinetics. 23(5) |
| ISSN: | 1880-0920 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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