Figure 1.

Schematic representation of the complex interplay between drug‐specific and system‐specific parameters driving hepatic CLp values. Parameters within circles are directly used in the physiologically based pharmacokinetic hepatic clearance model (e.g., dispersion model). Parameters in the purple circles represent composite parameters that are derived from the system‐specific parameters and the drug‐specific parameters indicated by the numbers in the subscripts. In children, each of the system‐specific parameters change with age, each represented by a lightning bolt. B:P, blood to plasma ratio; CLint, intrinsic metabolic clearance in the liver based on unbound drug concentrations; fu, unbound drug fraction in plasma; MPPGL, microsomal protein per gram of liver.