Table II.

Population Pharmacokinetic Model Parameters of the Structural Base Model (Without Covariates) and the Final Model (with Covariates) for Vancomycin in Normal Weight, Overweight, and Obese Children and Adolescents Aged 1–18 Years Old with and without Renal Impairment

Parameter	Structural model (RSE %)	Final model (RSE %) [95% CI]
Fixed effects
CL (L/h)	2.17 (2)	-
TVCL $\mathbf{\times }{\left(\frac{\mathbf{TBW}}{\mathbf{22.1}}\right)}^{\mathbf{\theta }\mathbf{1}}\mathbf{\times }\left(\frac{{\mathbf{\text{SCHW}}}^{\mathit{a}}}{\mathbf{100}}\right)$
TVCL (L/h)	-	2.12 (1) [2.07–2.17]
θ1	-	0.745 (2) [0.720–0.768]
V1 (L)	5.27 (8)	-
TVV1 $\mathbf{\times }\left(\frac{\mathbf{TBW}}{\mathbf{22.1}}\right)$
TVV1 (L)	-	8.90 (3) [8.50–9.33]
Q (L/h)	2.24 (4)	-
TVQ $\mathbf{\times }{\left(\frac{\mathbf{TBW}}{\mathbf{22.1}}\right)}^{\mathbf{\theta }\mathbf{2}}$
TVQ (L)	-	1.55 (5) [1.44–1.65]
θ2	-	0.599 (9) 0.517–0.685]
V2 (L)	11.9 (8)	-
TVV2 $\mathbf{\times }\left(\frac{\mathbf{TBW}}{\mathbf{22.1}}\right)$
TVV2 (L)	-	12.3 (6) [11.2–13.6]
Inter-individual variability (IIV, %) b,c
CL	52.8 (3)	28.7 (5) [27.1–30.7]
Covariance IIV CL-V2	-	−0.085 [−0.11 to −0.062]
V2	89.4 (7)	110 (7) [95.9–130]
Residual variability
Proportional errord,e	0.107 (7)	0.0789 (6) [0.0746–0.0836]
OFV	−1886.4	−5222.5

^aSchwartz value is maximized to 120 mL/min/1.73 m²

^bShrinkage of inter-individual variability in the final model is 24% for CL, 57 % for V2

^cCoefficient of variation, calculated by $\sqrt{\left({\mathit{e}}^{{\mathit{\omega }}^{\mathbf{2}}}\mathbf{-}\mathbf{1}\right)}$

^dProportional error is shown as σ

^eEpsilon shrinkage for the final model is 16%

CI confidence interval obtained from sampling importance resampling (SIR) procedure, CL clearance, OFV objective function value, Q inter-compartmental clearance between V1 and V2, RSE relative standard error based on the covariance step in NONMEM, SCHW creatinine clearance based on bedside Schwartz equation, TBW total body weight, TVCL typical value of CL for an individual weighing 22.1 kg and with creatinine clearance of 100 mL/min/1.73 m², TVQ typical value of Q for an individual weighing 22.1 kg, TVV1 typical value of V1 for an individual weighing 22.1 kg, TVV2 typical value of V2 for an individual weighing 22.1 kg, V1 volume of distribution of central compartment, V2 volume of distribution of the peripheral compartment