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An integrated modelling approach for in vitro to in vivo extrapolations

Abstract : Predicting in vivo drug toxicity from in vitro testing requires modelling those processes that are not reproduced in vitro. The most obvious difference between the two settings is the lack of integrated absorption, distribution, metabolism and excretion (ADME) that govern target tissue exposure in vivo. For equal input doses, the concentrations to which in vitro systems are exposed may not correspond to those found in vivo. The partners of the European project PREDICT-IV in charge of modelling develop prediction models for ADME processes and integrate them into generic physiologically based pharmacokinetic (PBPK) models. Examples of simulations of concentration-time profiles for diazepam and ciclosporin A, in various human or rat organs and tissues, are presented here. The in vivo toxicity of drugs will be forecasted by coupling the predicted target tissue concentration profiles to dose-response relationships observed in vitro. Human variability will be evaluated for each component of the approach.
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  • HAL Id : ineris-00961757, version 1
  • INERIS : EN-2011-349

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Frédéric Y. Bois, Dany Habka, Céline Brochot. An integrated modelling approach for in vitro to in vivo extrapolations. ALTEX - Alternatives to Animal Experimentations, 2010, 27 (Special issue Proceedings), pp.103-108. ⟨ineris-00961757⟩

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