… known to affect pharmacokinetics (PKs; bottom-up). This was … cases was done by evaluating
difference in fit (DFFITS k ), Cook’… These were a combination of caffeine phenotyping studies …

… Physiologically based pharmacokinetic (PBPK) models combining both … out modeling
approach, combining bottom-up in vitro-based predictions with limited top-down fitting of key model …

… on a series of model fitting processes mostly based on statistical … could be kinetically combined.
Although this tissue lumping … be reconciled with a top-down mPBPK analysis as shown in …

… 1, 2, 7 or by bottom-up approaches using primarily preclinical … new top-down approach and
to compare this approach with … Further, we adjusted the CL for both models to fit the results to …

… ) combined with the bottom-up approach may improve the … substrates using a combined
bottom-up and top-down approach. We used … Goodness-of-fit plots used throughout the model …

… simplifies the process of fitting PBPK models to available data, enabling a top-down …
top-down and bottom-up approaches, the middle-out approach, which combines both approaches, …

… impact of single and or combined intrinsic and extrinsic factors … via a hybrid bottom-up and
top-down strategy the effect of DDI … In addition, the model was verified by fitting the predicted …

… top down’ approach) or based on our general knowledge of the human physiology and its
mechanisms (‘bottom up’ approach… modelling were made based on defining and combining …

… simplified models fitted in preclinical species for each of the 3 compounds ...........................................................................................................
150 Table 4.5: Best models after fitting all models …

… high-performance liquid chromatography combined with mass … and the other reviewing it
for accuracy and goodness of fit. … a purely bottom-up approach for modeling absorption and …