Pharmacokinetic analysis of transcellular transport of quinidine across monolayers of human intestinal epithelial Caco-2 cells

Biological & Pharmaceutical Bulletin
Kazuya IshidaYukiya Hashimoto

Abstract

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 100 nM-100 microM. 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 100 microM than 100 nM. 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 100 microM. 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 degrees C, and was decreased at low temperature (4 degrees C). 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 d...Continue Reading

References

Sep 1, 1976·Clinical Pharmacology and Therapeutics·C T UedaB S Dzindzio
Apr 1, 1984·Journal of Clinical Pharmacology·E M Vaughan Williams
Mar 1, 1980·Clinical Pharmacokinetics·H R OchsE Woo
Jan 1, 1998·The New England Journal of Medicine·A A Grace, A J Camm
Jul 28, 2001·Clinical Pharmacokinetics·G E Schumacher, J T Barr
Mar 16, 2002·Life Sciences·Kohji TakaraKatsuhiko Okumura
Jun 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Stephan R VavrickaKarin Fattinger
Jan 7, 2005·Biological & Pharmaceutical Bulletin·Tetsuya AibaYukiya Hashimoto

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Citations

Jul 5, 2011·European Journal of Drug Metabolism and Pharmacokinetics·Anand G PatilAnagha Damre
Nov 6, 2007·Biological & Pharmaceutical Bulletin·Mari TakaaiYukiya Hashimoto
Apr 2, 2009·Biological & Pharmaceutical Bulletin·Kazuya IshidaYukiya Hashimoto
Aug 6, 2010·Biological & Pharmaceutical Bulletin·Miki MasagoYukiya Hashimoto
Nov 30, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Benjamin WuytsPatrick Augustijns
May 14, 2011·Biopharmaceutics & Drug Disposition·Asuka HorieYukiya Hashimoto
Sep 13, 2013·Drug Metabolism and Pharmacokinetics·Miki FukaoYukiya Hashimoto
May 31, 2013·Drug Metabolism and Pharmacokinetics·Kazuya IshidaYukiya Hashimoto
Mar 4, 2008·Pharmaceutical Research·Kathryn Whitehead, Samir Mitragotri
Mar 11, 2010·Clinical Pharmacokinetics·Joseph D MaAnne N Nafziger

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