Figure 4.

The prediction error (PE) of the total (bound and unbound) drug plasma clearance (CLp) predictions for scenarios in which model and test drugs are exclusively metabolized by one isoenzyme (fmA_adult = 100%) and exclusively binding to human serum albumin (a) or to alpha‐1 acid glycoprotein (b). The boxplots represent the minimum, firth quartile, median, third quartile, and maximum PE and are categorized by low (green), intermediate (blue), and high (pink) adult extraction ratio (ER) of the model drug and low (light color), intermediate (intermediate color), and high (dark color) adult extraction ratio of the test drug. For each age, the lowest, intermediate, and highest isoenzyme ontogeny values (percentage of adult CLint,mic) reported for the 15 isoenzymes are shown. The intermediate isoenzyme ontogeny was defined as the isoenzyme ontogeny value the closest to the mean of the lowest and highest isoenzyme ontogeny values for a specific age. Low, intermediate, and high extraction ratio correspond to extraction ratio ≤30%, 30% < extraction ratio ≤70% and extraction ratio >70%, respectively. The vertical solid black line indicates a PE of 0. The dotted black and dotted red lines indicate PE intervals of +/‐ 30% and +/‐ 50%, respectively. Note that the x‐axes are different for different ages.