Fig. 3.

Estimated in vivo FMO3 ontogeny functions by the mechanistic PPK model of risdiplam. Predictions of in vivo FMO3 ontogeny by the six mechanistic PPK models of risdiplam are shown with solid lines, between 2 months and 50 years of age. The in vivo FMO3 ontogeny functions represent the predicted fraction of adult’s FMO3 activity based on the scaled CL_int and accounting for age-dependent liver weight and MPPGL. The hepatic CYP3A4 ontogeny according to Upreti and Wahlstrom [19] (black dotted lines) is shown as a reference. The number of subjects in the analysis dataset between 1–2, 2–3, 3–4 and 4–5 months of age are indicated. Dotted lines in the 1–2 months age group represent extrapolations by these six FMO3 in vivo ontogeny models. FMO3 flavin-containing mono-oxygenase 3, PPK population pharmacokinetic, CL_int intrinsic clearance, MPPGL microsomal protein per gram of liver, CYP cytochrome P450