Exact kinetic analysis of passive transport across a polarized confluent MDCK cell monolayer modeled as a single barrier

Journal of Pharmaceutical Sciences
Thuy Thanh TranJ Bentz

Abstract

Knowledge of the passive permeability coefficient for new drugs is useful for estimating the fraction absorbed across the gastrointestinal tract. The commonly used approximate formula for the passive permeability coefficient is based on the initial rate of permeation across cell monolayers, requires measurement during the linear phase of permeation, and is not applicable when there is significant back flux of compound or mass balance problem. To develop a rigorous equation that can be used at any time point, i.e., that is valid outside of the linear phase, the mass action equations were integrated for a standard single barrier model of passive permeability. The simple analytical solution found also allows correction for both loss of drug (e.g., due to binding and/or hydrolysis) and sampling volume loss for multiple time point experiments. To test this equation, we measured the passive permeation of three well characterized drugs (amprenavir, quinidine, and loperamide) across confluent monolayers of MDCKII-hMDR1 cells. The potent P-glycoprotein inhibitor GF120918 was used to inhibit P-glycoprotein activity, so only passive permeability was determined. Dramatically different time-dependent behavior was observed for the three comp...Continue Reading

Citations

Mar 31, 2012·Expert Opinion on Drug Metabolism & Toxicology·Travis T WagerPatrick Trapa
Apr 25, 2008·Expert Opinion on Drug Metabolism & Toxicology·Huadong SunK Sandy Pang
Feb 13, 2016·Journal of Pharmaceutical Sciences·Patrick E TrapaStefan J Steyn
May 10, 2008·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Dorien GroenendaalElizabeth C M de Lange
Dec 25, 2009·Basic & Clinical Pharmacology & Toxicology·Aki T HeikkinenJukka Mönkkönen
May 16, 2014·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Houfu LiuJasminder Sahi
Jan 10, 2012·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Simon TaylorJason Witherington
Dec 30, 2014·International Journal of Pharmaceutics·Grace A LedetLevon A Bostanian
Jan 13, 2006·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·John P Keogh, Jeevan R Kunta
Oct 31, 2007·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·P Jeffrey, S G Summerfield
Jan 19, 2006·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·I González-AlvarezM Bermejo
Nov 20, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Zhou MengJoe Bentz
Oct 13, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Huadong Sun, K Sandy Pang
Dec 31, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jinqiang ZhangZiqiang Cheng
Dec 18, 2008·The Journal of Pharmacology and Experimental Therapeutics·Aki T HeikkinenTimo Korjamo
Jan 29, 2020·Nature Biomedical Engineering·Richard NovakDonald E Ingber
Nov 12, 2009·Journal of Medicinal Chemistry·Karen A EvansFrancisco Javier Colilla
Feb 28, 2009·Molecular Pharmaceutics·Victoria E Thiel-DembyJoseph W Polli

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