Influence of protein binding and lipophilicity on the distribution of chemical compounds in in vitro systems

Toxicology in Vitro : an International Journal Published in Association with BIBRA
Michael Gülden, Hasso Seibert

Abstract

Concentration-effect relationships determined in vitro depend not only on the activity of the chemical compounds or the sensitivity of the targets but also on the distribution of the compounds in the in vitro systems. In cell cultures, protein binding and lipid/water partition can be major determinants of distribution. Both are dependent on substance-specific factors, such as affinity to protein binding sites and lipophilicity, and on system-specific factors, such as protein concentration and lipid/water relationships. With this in mind, an algorithm has been developed that relates the total concentration of a compound to the free concentration in the aqueous phase. This algorithm can be used to describe theoretically the quantitative influence of the various factors relevant for distribution on concentration-response relationships. Conditions can be defined where protein binding and lipid/water partition are quantitatively important and have to be considered when comparing EC(50) values obtained in different in vitro systems. Provided that substance- and system-related parameters are known, the algorithm can be used in comparative cell toxicology to estimate equivalent effective concentrations for differently composed systems.

References

Aug 1, 1985·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·A B Fischer
Jan 1, 1987·Toxicology in Vitro : an International Journal Published in Association with BIBRA·J BenoitJ Wepierre
Aug 1, 1995·Toxicology in Vitro : an International Journal Published in Association with BIBRA·J M Frazier
Aug 1, 1994·Toxicology in Vitro : an International Journal Published in Association with BIBRA·H H BohetsP J Dierickx

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Citations

May 30, 2001·Toxicology in Vitro : an International Journal Published in Association with BIBRA·M GüldenH Seibert
Jul 7, 2007·Journal of Toxicology and Environmental Health. Part a·Joop L M HermensThomas L ter Laak
Dec 10, 2009·Gastroenterology Research and Practice·G DesolneuxA Hamy
Feb 8, 2014·Archives of Toxicology·Katrin KittlerDominique Hurtaud-Pessel
Aug 24, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Robert D Combes
Jun 7, 2012·Critical Reviews in Toxicology·Miyoung YoonHarvey J Clewell
Feb 14, 2015·In Vitro Cellular & Developmental Biology. Animal·Joshua A HarrillWilliam R Mundy
Dec 3, 2013·Toxicology·Michael GüldenHasso Seibert
Jul 13, 2013·Toxicology and Applied Pharmacology·Mats F NilssonWilliam S Webster
Sep 5, 2009·Environmental Science and Pollution Research International·Bertram KuchKarl Theo von der Trenck
Nov 1, 2013·Drug and Chemical Toxicology·Ufuk ErenberkUlkan Kilic
Apr 7, 2007·Alternatives to Laboratory Animals : ATLA·Michael Gülden, Hasso Seibert
Mar 9, 2006·Alternatives to Laboratory Animals : ATLA·Sandra CoeckeAndrew Worth
Feb 3, 2007·Alternatives to Laboratory Animals : ATLA·Robert CombesUNKNOWN FRAME
Oct 22, 2002·Environmental Science & Technology·Beate I Escher, Joop L M Hermens
Jul 23, 2019·Chemical Research in Toxicology·Fabian C FischerBeate I Escher
Mar 21, 2017·Chemical Research in Toxicology·Fabian C FischerBeate I Escher
Dec 16, 2004·Environmental Science & Technology·Minne B HeringaJoop L M Hermens

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