The top-down Finite Time Pharmacokinetic (FTPK) models vis-a-vis the bottom-up PBPK models in early drug development.

We used simulated data based on Finite Time Pharmacokinetics (FTPK) models to examine the relationship between the peak blood concentration and the fraction of dose absorbed. We also analyzed literature experimental data with top-down FTPK models. The analysis of the simulated data revealed that the peak blood drug concentration is proportional to the fraction of dose absorbed minus the drug eliminated from zero time up to the end of the absorption process. The analysis of literature experimental data provided reliable estimates for the number of input stages, their duration and their input rates. The top-down FTPK models can reliably guide the early phase of drug development. The estimate for the blood concentration value corresponding to the fraction of dose absorbed over the volume of drug distribution, FD/Vd, derived from the fitting of FTPK models to experimental data, is the ideal parameter for the assessment of the extent of absorption. The peak blood concentration value can also be used, although it is not ideal, as a metric of the extent of absorption rather than as a routinely used rate metric.