Physiologically Based Pharmacokinetic Modeling: Methodology, Applications, and Limitations with a Focus on Its Role in Pediatric Drug Development
Figure 7
Simulation results using the PK-Sim software of a PBPK model for sildenafil in children [53]. (a): Predicted age-dependent sildenafil hepatic clearance across different pediatric ages based on the clearance scaling module in PK-Sim software. (b): Age-related doses for oral sildenafil in children depending on the simulated age-related exposure (not shown) of sildenafil in a virtual pediatric population and the estimated exposure of the estimated doses of sildenafil in children between 3 months and 18 years. Potential pediatric doses based on simulations for sildenafil to achieve adult exposure: infants and children from 3 months to 4 years: 0.8 mg/kg; children from 5 to 8 years: 0.5 mg/kg; and children older than 8 years: 0.35 mg/kg as in adults. Box plots represent median, 25th, and 75th percentiles (box), 5th and 95th percentiles (error bar), and maximum and minimum values (x) of AUC0−∞ from 1000 simulations in each age group.
