Journal of Bioequivalence & Bioavailability

Confidence assessment of absorption/disposition modeling within PBPK modeling paradigm

7^th World Congress on Bioavailability & Bioequivalence: BA/BE Studies Summit

August 29-31, 2016 Atlanta, USA

Stephen Wang

Pfizer, USA

Posters & Accepted Abstracts: J Bioequiv Availab

Abstract:

The objective of this study was to assess the accuracy and precision of the Simcyp ADAM model to predict from a �??bottom-up�?? approach, the human absorption component within a physiologically-based pharmacokinetic profile. 21 literature compounds with respective in vitro Caco-2 permeability and aqueous solubility limits were inputted in ADAM along with clinical values for volume of distribution and clearance. In this fashion, we directly test the absorption component predicted by ADAM within the PBPK model. Simulated pharmacokinetic parameters (Tmax, Cmax and AUC0-�?) were compared to clinical parameters. With respect to Tmax predictions, 58% of the simulations had an error of less than 2-fold. For the compounds with error >2-fold, 75% were overpredicted. Predictions of Cmax showed that 48% of the simulations had an error of less than 2-fold. For the compounds with error >2-fold, the majority (90%) of the Cmax values were under-predicted. Similar to this, 43% of the AUC0-�? predictions had an error of less than 2-fold. For the compounds with error >2-fold, 83% were under-predicted. Taken together, caution must be exercised in the utilization of a �??bottom-up�?? PBPK model approach using limited in vitro permeability data and/or solubility limits to simulate the exposure in human.

Biography :

Email: Stephen.wang@pfizer.com