LAUSR

There has been an increasing interest in accurate prediction of human pharmacokinetics (PK) of drug candidates in order to reduce cost and increase productivity during research and development. Modeling efforts have primarily focused on predicting drug absorption after oral administration since it is the most desired route for small molecule drug delivery. Despite significant progress in the field, the fraction of dose absorbed (Fa) is still considered to be a challenging parameter to predict. In recent years compartment and transit models have become increasingly popular due to their effectiveness. A multi-compartment plug-flow based model in which the stomach is assigned as a single compartment has been built. However, this model was found to be less accurate in estimating stomach solubilization of basic drugs under certain conditions and leads to false-negative results. Therefore, a modified multi-compartment approach was developed by dividing the stomach into four compartments allowing the model to better mimic the physiological conditions. This approach was found to be more precise in estimating Fa for basic drugs compared to the previous approach. Based on this finding, it is believed the above approach should also be applicable to all compartmental based models when similar issues are encountered.