This paper focuses on a physiologically-oriented mathematical model aimed at studying the in vivo drug release, absorption, distribution, metabolism and elimination (ADME). To this purpose, the model accounts for drug delivery from an ensemble of non-eroding poly-disperse polymeric particles and the subsequent ADME processes. The model outcomes are studied with reference to three widely used drugs: theophylline, temazepam and nimesulide. One of the most important results of this study is the quantitative evaluation of the interplay between the release kinetics and the subsequent ADME processes. Indeed, it is usually assumed that in vivo drug release coincides with in vitro so that the effect exerted by the ADME processes is neglected. In addition, the proposed model may be an important tool for the design of delivery systems since, through proper changes, it could also account for different oral delivery systems.