The permeation of amphoteric drugs through artificial membranes--an in combo absorption model based on paracellular and transmembrane permeability

Journal of Medicinal Chemistry
Kin Y TamNa Sun

Abstract

The permeability characteristics of 33 amphoteric drugs (about 64% zwitterions at physiological pH) were studied using the parallel artificial membrane permeability assay (PAMPA) at pH 6.5. The PAMPA data were modified to include the paracellular permeability component found in cellular monolayers based on a newly generalized version of a popular model devised for Caco-2 cells. These "in combo" PAMPA data were used to predict the human absolute bioavailability of the ampholytes. The analysis produced a good fit, with only five outliers whose transport properties, could be rationalized by (a) nonpassive permeability processes, (b) metabolic instability, and (c) the possible sensitivity to microclimate pH effects in the case of acidic ampholytes. With the exception of two compounds, all of the ampholytes with bioavailability <50% were predominantly transported by the paracellular route, surprisingly with several of the compounds having molecular weights exceeding 350 Da.

References

Sep 12, 1978·Naunyn-Schmiedeberg's Archives of Pharmacology·D Winne
Nov 1, 1990·Journal of Pharmaceutical Sciences·K Takács-NovákG Szász
Jun 1, 1970·Journal of Pharmaceutical Sciences·S H Yalkowsky, G Zografi
May 1, 1995·The Journal of Pharmacy and Pharmacology·K Takács-NovákG Szász
Jun 1, 1997·The Journal of Antimicrobial Chemotherapy·R TengJ Vincent
Sep 16, 1999·International Journal of Pharmaceutics·L X Yu, G L Amidon
Dec 21, 2000·European Journal of Medicinal Chemistry·J WoutersB Masereel
Feb 20, 2002·Chemical Reviews·Alessandra PagliaraBernard Testa
Jan 8, 2003·Biopharmaceutics & Drug Disposition·Peter H Hinderling
Oct 31, 2003·Clinical Pharmacology and Therapeutics·Christer TannergrenHans Lennernäs
Mar 5, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Marival BermejoVirginia Merino
Apr 29, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Per E Nielsen, Alex Avdeef
Sep 14, 2004·Pharmaceutical Research·Niclas PetriHans Lennernäs
Oct 22, 2004·European Journal of Pharmacology·Hideyuki MotohashiKen-Ichi Inui
Mar 1, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Alex AvdeefStaffan Tavelin
Dec 13, 2005·Trends in Pharmacological Sciences·Pauline BreedveldJan H M Schellens
Feb 16, 2006·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Alex Avdeef, Oksana Tsinman
Mar 15, 2006·Naunyn-Schmiedeberg's Archives of Pharmacology·Ernst Petzinger, Joachim Geyer
Jul 4, 2006·The Journal of Antimicrobial Chemotherapy·Kenneth N Agwuh, Alasdair MacGowan
Aug 18, 2006·Journal of Medicinal Chemistry·Craig JamiesonGrant Wishart
Sep 7, 2007·Journal of Pharmaceutical Sciences·Alex AvdeefYukinori Yamauchi
Oct 31, 2007·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H Lennernäs
Nov 7, 2007·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Alex AvdeefKonstantin Tsinman
Apr 23, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·R Scott ObachNigel J Waters
Jul 29, 2008·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Eva M del AmoMarjo Yliperttula
Aug 6, 2008·Expert Opinion on Drug Metabolism & Toxicology·Graham Lappin, Lloyd Stevens
Apr 11, 2009·Journal of Pharmaceutical Sciences·Derek P ReynoldsAlanas Petrauskas

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Citations

Nov 6, 2010·Pharmaceutical Research·Xiangli LiuAlfred Fahr
May 15, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Gergely VölgyiKin Y Tam
Aug 26, 2011·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Matěj VelickýRobert A W Dryfe
Jun 10, 2011·Journal of Pharmaceutical and Biomedical Analysis·Na Sun, Alex Avdeef
Mar 8, 2011·Chemistry and Physics of Lipids·K CyprychM Przybylo
Jun 6, 2012·Biochimica Et Biophysica Acta·Oana CramariucIlpo Vattulainen
Mar 12, 2015·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·D SchönherrW Weitschies
Jun 2, 2017·Molecular Pharmaceutics·Hanah MesallatiLidia Tajber
Oct 19, 2016·Chemical Communications : Chem Comm·Anilkumar GunnamAshwini Nangia
Aug 4, 2018·Chemistry : a European Journal·Jiaxin QuanHaibing Li
Sep 7, 2017·Pharmaceutical Research·Hanah Mesallati, Lidia Tajber
Jun 30, 2018·Molecular Pharmaceutics·Enikő BorbásZsombor K Nagy

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