Fig. 1.
Prediction of the age down to which the pediatric covariate function for CYP3A-mediated midazolam clearance can be used to accurately scale clearance of CYP3A substrates with specific drug properties. Extraction ratio values of the tested CYP3A substrates are plotted versus the fraction unbound (fu) of the test drugs in adults. The color scheme was obtained from the published framework (7) and represents hypothetical model-test drug combinations that lead to systematically accurate scaling of clearance in children down to 1 day (green), 1 month (purple), 6 months (orange), 1 year (blue), 2 years (pink), and 5 years of age (yellow). Red indicates that scaling is not systematically accurate in children of 5 years and younger. The black data points represent the included test drugs and their extraction ratio and fu values. Panel a shows drugs binding to albumin (HSA), while panel b shows drugs binding to α1-acid glycoprotein (AAG). Modified from Calvier et al. (7) (with permission)