Fig. 2.

Scaled and reported clearance values versus body weight for various CYP3A substrates. Clearance (or apparent clearance) values are based on the between-drug extrapolation of the pediatric covariate function for CYP3A-mediated midazolam clearance and reported adult clearance values (black) and based on reported pediatric clearance values in literature (gray), for sildenafil (a), atorvastatin (b), quinidine (c), sirolimus (d), sufentanil (e), tacrolimus (f), tamsulosin (g), and vincristine (h). The vertical dotted line (gray) indicates the body weight down to which systemically accurate clearance scaling is predicted to be possible according to the framework (7). For the reported clearance values the following is depicted: a Mean sildenafil clearance (line) with minimal and maximal reported values (gray area). b Typical atorvastatin clearance (line) ± 46.3% (%CV, gray area). c Mean quinidine clearance (line) ± 2 SD (gray area) and individual-reported clearances (closed circles). d Individual-reported sirolimus clearances (closed circles). e Mean sufentanil clearance (line) ± 2 SD (gray area). f Typical tacrolimus clearance (line) ± 41.6% (%CV, with $\mathrm{CV}=\sqrt{e^{{\sigma }^2}-1}$, and σ² = 0.16, gray area). g Typical tamsulosin clearance (line) ± 54.4% (%CV, gray area). h Individual-reported vincristine clearances, corrected for body surface area (closed circles)