RRC ID 62788
著者 Togami K, Tosaki Y, Chono S, Morimoto K, Hayasaka M, Tada H.
タイトル Enantioselective uptake of fexofenadine by Caco-2 cells as model intestinal epithelial cells.
ジャーナル J Pharm Pharmacol
Abstract OBJECTIVES:Fexofenadine contains a chiral carbon in its chemical structure and is orally administered as a racemic mixture. This study evaluated the selective uptake of fexofenadine enantiomers by Caco-2 cells as a model of intestinal epithelial cells.
METHODS:R(+)-fexofenadine or S(-)-fexofenadine was applied to Caco-2 cells, followed by incubation. After incubation, the amounts of fexofenadine enantiomers in cells were determined. The kinetic parameters for the uptake of fexofenadine enantiomers by Caco-2 cells were estimated using the Michaelis-Menten equation.
KEY FINDINGS:The transporter-mediated uptake rate of R(+)-fexofenadine was 1.7-fold higher than that of S(-)-fexofenadine. The difference in transporter-mediated R(+)-fexofenadine and S(-)-fexofenadine uptake was completely diminished under ATP-depleted conditions and in the presence of organic anion transporter peptide (OATP) inhibitors. Also, a Dixon plot showed that each fexofenadine enantiomer was competitively inhibited by the other enantiomer. The ratio of R(+)-fexofenadine uptake to S(-)-fexofenadine uptake in the case of a racemic mixture was higher than that in the case of a single enantiomer.
CONCLUSION:This study suggested that the selective absorption of fexofenadine enantiomers by intestinal epithelial cells might have been due to the selective uptake mediated by OATPs and that the difference in intestinal absorption was enhanced with a racemic mixture.
巻・号 65(1)
ページ 22-9
公開日 2013-1-1
DOI 10.1111/j.2042-7158.2012.01569.x
PMID 23215684
MeSH Adenosine Triphosphate / antagonists & inhibitors Adenosine Triphosphate / metabolism Anti-Allergic Agents / chemistry Anti-Allergic Agents / metabolism* Binding, Competitive Biological Transport, Active / drug effects Caco-2 Cells Enterocytes / drug effects Enterocytes / metabolism* Histamine H1 Antagonists, Non-Sedating / chemistry Histamine H1 Antagonists, Non-Sedating / metabolism* Humans Intestinal Absorption* / drug effects Kinetics Membrane Transport Modulators / pharmacology Organic Anion Transporters / antagonists & inhibitors Organic Anion Transporters / metabolism* Proton Ionophores / pharmacology Stereoisomerism Terfenadine / analogs & derivatives* Terfenadine / chemistry Terfenadine / metabolism Uncoupling Agents / pharmacology
IF 2.571
リソース情報
ヒト・動物細胞 CACO-2(RCB0988)