Abstract
Assessing the oral drug suitability of compounds as early as possible within drug discovery is an important objective. This study describes a methodology that attempts to simplify the evaluation of compounds based on their in vivo quantity levels within a mammalian body, represented using a mathematical model that imposes a time limitation on oral absorption and assumes non-instantaneous drug distribution between plasma and tissue. This simplification results in two new oral drug suitability parameters that can quantitatively relate oral dose to in vivo exposure for compounds with vastly different tendencies in terms of absorption into, and elimination from, the body. Consequently, the complexities associated with evaluating a compound's oral drug suitability are simplified to an assessment of these two new parameters. Application of this methodology at the virtual design stage is discussed, along with functionality that accounts for uncertainty related to a compound's distribution kinetics and errors associated to in silico QSAR predictions for the required input data.