Pharmacokinetic Analysis of Transcellular Transport of Quinidine across Monolayers of Human Intestinal Epithelial Caco-2 Cells(Biopharmacy)

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概要

• 論文の詳細を見る

• To investigate the mechanism responsible for the intestinal absorption of a lipophilic organic cation, quinidine, we performed a pharmacokinetic analysis of transcellular transport across Caco-2 cell monolayers grown on a porous membrane. Basolateral-to-apical transport of the drug was almost constant in the concentration range of 100nM-100μM. Transcellular transport was greater in the apical-to-basolateral direction than in the opposite direction. Apical-to-basolateral transport was greater at a concentration of 100μM than 100nM. The calculated influx clearance value of the apical membrane was much greater than the other influx/efflux clearance values of cell membranes, and was 5.6-fold the influx clearance value of the basolateral membrane at the drug concentration of 100μM. We also investigated the uptake of quinidine at the apical membrane of Caco-2 cells grown on plastic dishes. The uptake was markedly increased by alkalization of the apical medium at 37℃, and was decreased at low temperature (4℃). In addition, it was inhibited by diphenhydramine and levofloxacin, but not by carvedilol, rifamycin SV, or L-carnitine. These findings indicated that the influx at the apical membrane was the direction-determining step in the transcellular transport of quinidine across Caco-2 cell monolayers, and that some specific transport system was involved in this influx.

• 公益社団法人日本薬学会の論文
• 2006-03-01

著者

• HASHIMOTO Yukiya

  Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University

• Hashimoto Y

  Graduate School Of Pharmaceutical Sciences Kyushu University

• Hashimoto Yuichi

  Institute Of Molecular & Cellular Biosciences University Of Tokyo

• Harada Yuichi

  Center For Influenza Virus Research National Institute Of Infectious Diseases

• Ishida Kazuya

  Graduate School Of Medicine And Pharmaceutical Sciences Univ. Of Toyama

• Hashimoto Yukiya

  Graduate School Of Medicine And Pharmaceutical Sciences Univ. Of Toyama

• TAKAAI Mari

  Graduate School of Pharmaceutical Sciences, University of Toyama

• Hashimoto Y

  Institute Of Molecular & Cellular Biosciences The University Of Tokyo

• Takaai Mari

  Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

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