Quantitative structure–pharmacokinetic relationship modelling

摘要: Abstract This article presents the current methods in quantitative structure–pharmacokinetic relationship (QSPkR) modelling along with examples using chemicals of toxicological significance. The common method involves: (i) collecting pharmacokinetic data or determining parameters (e.g. elimination half-life, volume distribution) by fitting to experimental data; and (ii) associating them structural features a Free–Wilson model. Such QSPkRs have been developed for few series but their usefulness is limited exposure scenario conditions under which were originally collected. alternative approach involves development structure–property (QSPR) models parameters, blood:air partition coefficient, tissue:blood maximal velocity metabolism Michaelis affinity constant, physiologically-based (PBPK) are useful conducting species, route, dose extrapolations tissue chemicals. Mechanistic QSPRs available predicting coefficients from molecular structure information chemicals, whereas such approaches not currently hepatic parameters. However, at present time, pharmacokinetics inhaled volatile organic can be simulated adequately considering physiological limits extraction ratio (0–1) structure-based estimates PBPK state-of-the-art will advance other chemical-specific models. Integrated QSPR–PBPK should facilitate identification family that possess desired properties bioaccumulation blood concentration profile both test animals humans.