Tamara van Donge

Chapter 7 146 Supporting Information 2 Sensitivity analysis was performed where different Vds are compared, namely 0.3 L/kg, 0.5 L/kg and 0.8 L/kg. Additionally, results of Vd starting at 0.7 L/kg and decreasing with 10% over the study period are shown. Finally, the percentage difference between the final model and combined model (developed dataset + validation dataset) are illustrated. Model parameters of final developed model (Vd = 0.7 L/kg) Percentage difference with Vd set at 0.7 L/kg % differ- ence with combined model Vd of 0.3 L/kg Vd of 0.5 L/kg Vd of 0.8 L/kg 10% decrease over PNA Population parameters Crea birth (mg/dl) 0.597 0.2 0 0.2 -0.2 6.37 Kin production (mg/day) 3.55 -58.3 -26.8 13.2 1.9 -17.5 CL BL (L/day) 0.075 -5.9 -1.1 -2.7 2.52 -4.9 Emax (day -1 ) 0.874 -57.7 -27.0 14.4 1.37 -2.1 t 50 (days) 21.1 1.4 3.3 1.4 3.2 1.9 Hill 1.31 -3.0 0.8 -1.5 2.29 1.5 Inter-individual variability Crea birth 0.252 -1.2 -0.4 -1.6 -0.8 1.6 CL BL 0.255 3.9 -4.3 5.9 -8.6 10.2 t 50 0.49 -1.4 -1.2 -0.8 -0.6 -7.8 Hill 0.481 0 0.21 -0.2 -1.0 9.9 Covariate parameters IBU effect on CL BL (no/yes) 2.73/2.55 -76.9/-79.1 -32.2/-34.1 21.2/20.8 6.2/4.7 24.9/20.8 GA effect on t 50 -2.35 0.8 -3.4 1.7 2.1 25.9 MOD effect on t 50 -0.24 0 2.1 -3.3 -0.4 28.0 GA effect on Crea birth 1.6 0.6 2.5 -0.6 -1.25 -17.5 Residual variability Proportional error 0.11 0 0 0 0 1.8