Table 2.

Typical kinetic parameters (θ), unexplained inter-individual variability estimated as variance (ω²), and residual variability estimated as variance (σ²) obtained from the pharmacometric analysis

Kinetic parameter	Estimate	95% CI	RSE (%)
Clearance, CL = θ1 × (IBW/75)^θ7 [L/h]
θ1	3.67	3.25, 4.26	6.5
ω12	0.0225 (ω1: 15.1% CV)	0.00322, 0.0419	24.9
Central volume of distribution, V2 = θ2 × (AGE/29)^θ8 [L]
θ2	69.5	54.5, 84.8	11.1
ω22	0.21 (ω2: 48.3% CV)	0.0342, 0.338	18.3
Peripheral volume of distribution, V3 = θ3 × (IBW/75)^θ9 [L]
θ3	235	177, 312	12.6
First-order absorption rate constant, ka = θ4 [h−1]
θ4	0.924	0.722, 1.14	11.1
Distribution clearance, Q = θ5 [L/h]
θ5	28.2	24.7, 33.2	6.7
Baseline, BSL = θ6 [µmol/L]
θ6	2.77	2.44, 3.15	6.5
ω32	0.0799 (ω3: 28.8% CV)	0.0361, 0.123	13.6
Covariate ideal body weight (IBW) on CL = θ7
θ7	1.4	0.897, 1.99	18
Covariate age on V2 = θ8
θ8	− 1.86	− 2.54, − 1.20	15.4
Covariate ideal body weight (IBW) on V3 = θ9
θ9	1.27	0.225, 2.43	35.3
Residual variability model
σproportional,baseline	15.5% CV	0.124, 0.188	10.8
σadditive,baseline	0.267 µmol/L	Fixeda	53.2
σproportional	25.6% CV	0.237, 0.274	3.8

IBW ideal body weight, CV coefficient of variation, RSE relative standard error (reported on standard deviation (SD) scale for variability parameters), CI 95% confidence interval determined by a non-parametric bootstrap analysis (n = 1000)

The transformation of ω² to coefficient of variation was calculated by $\sqrt{\left(e^{{\omega }^2},-,1\right)}\times 100\%$

^aFixed to final estimate during bootstrap to increase model stability