Directional Transcellular Transport of Bisoprolol in P-glycoprotein-expressed LLC-GA5-COL150 Cells, but not in Renal Epithelial LLC-PK1 Cells

• TAHARA Katsutoshi

  Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

• KAGAWA Yuka

  Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

• TAKAAI Mari

  Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

• TAGUCHI Masato

  Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

• HASHIMOTO Yukiya

  Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

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.<br>

収録刊行物

• Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ

  Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 23 (5), 340-346, 2008

  日本薬物動態学会

キーワード

• bisoprolol
• cationic drugs
• renal secretion
• transcellular transport
• kinetic analysis
• kidney epithelial cell line

詳細情報

• CRID: 1390001205180490496
• NII論文ID: 10024384607
• NII書誌ID: AA1162652X
• DOI: 10.2133/dmpk.23.340
• COI: 1:CAS:528:DC%2BD1cXhsFahsLjO
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715302081?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715302081?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2009106686
• 本文言語コード: en
• データソース種別:
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  • Crossref
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