Simulation models to predict oral drug absorption from in vitro data

Abstract Comprehensive models of oral drug absorption which allow direct extrapolation to humans from in vitro measured data have the potential to provide tremendous benefits to the discovery process and as a result, significantly impact potential profitability. A fully functional model would allow the prediction of the human oral absorption of drugs, or toxins, using relatively simple in vitro experiments. The most successful models should predict both the extent and rate of drug absorption and ideally, should include estimates of preabsorptive metabolism or degradation. Typical in vitro experiments (or predicted values) would include determination of solubility at several pH conditions, and a measure of the drug permeability in intestinal tissue. Such models, especially with the use of cultured cells as a replacement for animal tissue, have the potential to significantly reduce or eliminate the use of animals to predict oral drug absorption. Although none of the models available at the time of this review have proven to be ‘flawless’ in their predictive abilities, the progress that has been made over the past 20 years suggests a time when the characterization of the absorption properties of new chemical compounds will be routine in the drug discovery process.