A population approach to in vitro–in vivo correlation modelling for compounds with nonlinear kinetics

Developing an In Vitro–In Vivo Correlation (IVIVC) model is becoming an important part of the drug development process. Traditional methods such as deconvolution and convolution make the assumption of linearity of the system being studied and are, therefore, unsuitable for use with compounds exhibiting nonlinear kinetics. This study proposes the use of a compartmental approach which may be based on systems of differential equations, a method which can comfortably accommodate nonlinearity. This technique can easily be implemented using existing NONMEM libraries and is an accurate, fast and straightforward method of developing an IVIVC model.