Directional transcellular transport of bisoprolol in P-glycoprotein-expressed LLC-GA5-COL150 cells, but not in renal epithelial LLC-PK1 cells

Katsutoshi Tahara, Yuka Kagawa, Mari Takaai, Masato Taguchi, Yukiya Hashimoto*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

16 被引用数 (Scopus)

抄録

To evaluate the mechanism responsible for the tubular secretion of bisoprolol, we compared transcellular transport of bisoprolol with that of tetraethylammonium (TEA), cimetidine, and quinidine across LLC-PK1 cell monolayers grown on porous membrane filters. TEA and cimetidine were actively transported in the basolateral-to-apical direction by the specific transport system. Pharmacokinetic analysis indicated that basolateral influx and apical efflux were cooperatively responsible for the directional transport of TEA and cimetidine. Lipophilic cationic drugs, quinidine, S-nicotine, and bisoprolol, significantly diminished basolateral influx and apical efflux clearance of cimetidine. However, transcellular transport of quinidine in the basolateral-to-apical direction was similar to that in the opposite direction in LLC-PK1 cells. In contrast, quinidine was transported actively in the basolateral-to-apical direction in P-glycoprotein-expressed LLC-GA5-COL150 cells. Pharmacokinetic analysis indicated that P-glycoprotein increased the apical efflux of quinidine and also decreased the apical influx of the drug. Basolateral-to-apical transport of bisoprolol was also similar to apical-to-basolateral transport in LLC-PK1 cells, whereas the drug was directionally transported from the basolateral to the apical side in LLC-GA5-COL150 cells. These results suggested that bisoprolol was not significantly transported via transport systems involved in the directional transport of TEA and cimetidine, but that P-glycoprotein was responsible for the directional transport of bisoprolol as well as quinidine in renal epithelial cells.

本文言語英語
ページ(範囲)340-346
ページ数7
ジャーナルDrug Metabolism and Pharmacokinetics
23
5
DOI
出版ステータス出版済み - 2008

ASJC Scopus 主題領域

  • 薬理学
  • 薬科学
  • 薬理学(医学)

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