Prediction of Human Oral Plasma Concentration-Time Profiles Using Preclinical Data

Background and Objectives: Empirically based methods remain one of our tools in human pharmacokinetic predictions. The Dedrick approach and the steady-state plasma drug concentration (Css)-mean residence time (MRT) approach are based on the assumption that concentration-time profiles are similar among species, including man, and that curves derived from a variety of animal species can be superimposed after mathematical transformation. In the Dedrick approach the transformation is based on the slope and intercept of the allometric relationship. The Css-MRT approach is based on the implementation of measured animal and predicted human MRT and dose/volume of distribution at steady state (Vss). The aims of the present study were to compare the predictive performance of concentration-time profiles obtained by these approaches, to evaluate the prediction of individual pharmacokinetic parameters by these approaches and to further refine these approaches incorporating the experience from our previous work.