A unified algorithm for predicting partition coefficients for PBPK modeling of drugs and environmental chemicals

Dose Selection Based on Physiologically Based Pharmacokinetic (PBPK) Approaches

“…The tissue composition-based equations described above have been designed to describe specific interactions. Recently, unified algorithms combining these different processes have been developed to facilitate their application (6,(46)(47)(48). Several studies have been performed to explore predictability of the different mechanistic approaches for Kp prediction using diverse drug datasets, with varying degrees of accuracy (8,10,11,(48)(49)(50)(51)(52)(53).…”

Non-animal approaches for toxicokinetics in risk evaluations of food chemicals

“…To further improve and integrate these in vitro approaches, recent research efforts have focussed on developing organ-ona-chip models, in which cells or co-cultures of cells are grown in microfluidic devices in continuously perfused chambers in order to model physiological functions of tissues and organs (Jiang et al, 2016). Other important developments in recent years have been the integration of in vitro kinetic data with in silico physiologically based pharmacokinetic (PBPK) models, with the aim to simulate the kinetics of chemicals in organisms (Bessems et al, 2014;Bois et al, 2010;Yoon et al, 2012), and the development of quantitative structure activity relationships (QSARs) to predict kinetic data based on chemical structures and their physicochemical characteristics as part of read-across approaches (Peyret and Krishnan, 2011;Peyret et al, 2010;Rodgers and Rowland, 2006).…”

Modeling Pharmacokinetics

“…Molecular simulation (quantum chemistry) models can also be used [39,40], in particular for the difficult problem of metabolic parameters' estimation. QSARs are statistical models (often a regression) relating one or more parameters describing chemical structure (predictors) to a quantitative measure of a property or activity (here a parameter value in a PBPK model) [15,[41][42][43][44]. However, when predictive structure-property models are not available (as is often the case with metabolism, for example), the parameters have to be measured in vitro (for an extensive review see [45,46]) or estimated from in vivo experiments and are much more difficult to obtain.…”

“…A significant advance has been the development of quantitative structure-properties models for the chemical-dependent parameters of PBPK models (e.g., tissue affinities) [14,15]. Those developments are still ongoing and have led to large generic models which can give quick, even if approximate, answers to pharmacokinetic questions, solely on the basis of a chemical's formula and limited data [16][17][18].…”