Figure 4

PKPD modelling for the heart only and heart:liver models. (a) Schematic of the modelled system is shown where PDMS, cardiac, and liver compartments allow flow of terfenadine to and from the media compartment. Cardiac and liver compartments are capable of metabolizing terfenadine into fexofenadine and change in FPD is solely dependent on cardiac terfenadine concentration. Terfenadine PK and FPD profiles are plotted for predicted and observed data over 24 hours and are modelled in both heart only and heart:liver systems. Corresponding fexofenadine PK profiles can be found in Supplementary Fig. 2. *Parameter is defined by Eq. 2. (b) Published^21,22, mean Terfenadine PK profiles ± SD for Guinea pig, dog and humans were inputted into the model and corresponding mean FPD predicted values ± SD were simulated.