Table 3.

Summary of seven published population pharmacokinetic models of vancomycin in neonates

Model	A§	B§	C	D	E	F	G
Reference	Anderson et al., 2007 [8]	Allegaert et al., 2007 [9]	Kimura et al., 2004 [10]	Lo et al., 2010 [11]	Marqués-Miñana et al., 2010 [12]	> Grimsley et al., 1999 [17]	Capparelli et al., 2001 [13]
Patients	Premature neonates (PMA range 24–34 weeks)	Premature neonates (median PMA of 28 weeks, range 24–30 weeks)	Neonates and infants (PMA range 25.1–48.4 weeks)	Premature neonates (median PMA of 30 weeks; range 23.6–34 weeks)	Neonates and infants (PMA range 25.1–48.1 week)	Neonates and infants(GA range 25–41 weeks; PNA range 2–76 days)	Neonates and infants (GA 33.5 ± 6 weeks; PNA 70 ± 100 days)
Dosing regimen	PNA 1–7 days/serum creatinine value >71 μmol l−1: 15 mg kg−1 every 12 h	PNA 1–7 days/serum creatinine value >71 μmol l−1: 15 mg kg−1 every 12 h	PNA 1–7 days: 15 mg kg−1 every 12 h	See attached Table 3S1	See attached Table 3S2	15 mg kg−1 every 24 h – 15 mg kg−1 every 8 h	15 mg kg−1 every 24 h – 15 mg kg−1 every 12 h
	PNA > 7 days: 15 mg kg−1 every 8 h	PNA > 7 days: 15 mg kg−1 every 8 h	PNA > 7 days: 15 mg kg−1 every 8 h
Number of patients	214	249	19	116	111 (70 in building group and 41 in validation group)	59	374
Number of samples	604	648	88	835	–	347	1103
Sampling times	Trough and peak						Combination of sparse and intensive PK sampling
Structure model	One compartment model with first order elimination						Two compartment model with first-order elimination
Tested covariates	Weight, PMA, PNA, renal function, positive blood culture, positive ventilation, inotrope, NSAID, maternal betamethasone administration	Weight, PMA, SGA, renal function, NCOX, maternal betamethasone administration	Weight, PCA, PNA, GA, Apgar score, serum creatinine	Weight, PMA, PNA, SGA, serum creatinine, race, ventilation, NSAID	Weight, birth weight, PMA, PNA, GA, height, urine output, BSA, gender, concomitant drugs	Weight, PCA, GA, serum creatinine, nutrition,	Weight, PNA, GA, gender, serum creatinine, apgar5 score, ECMO
Significant covariate on CL	Weight, PMA, renal function*, positive pressure ventilation	Weight, PMA, renal function*, non-selective NSAIDs, SGA	Weight, PCA, serum creatinine	Weight, PMA, SGA	Weight, PMA, amoxicillin-clavulanic acid	Weight, serum creatinine	Weight, PNA, GA, serum creatinine
CL formula	3.83 × (weight/70)0.75 × (PMA3.68/(PMA3.68 + 33.33.68)) × (516 × EXP (0.00823 × ((PMA − 40)/52 − 40))/serum creatinine)/6) × Fventilation	1.58 × (weight/70)0.75 × (EXP(0.0456 × (PMA − 30))) × )) × (516 × EXP (0.00766 × ((PMA − 30)/52 − 40))/serum creatinine)/6) × FSGA × FNCOX	0.0323 × weight/Serum creatinine (PCA ≥ 34 weeks)	CL = 1.0 × (weight/70)0.75 × (PMA/30)3.16 × (FSGA)	0.00192 × PMA × (1 + 0.65 × amoxicillin-clavulanic acid) × weight	3.56 × weigh/serum creatinine	Weight × (0.028/serum creatinine + 0.000127 × PNA + FGA) + 0.006
			0.025 × weight/serum creatinine (PCA < 34 weeks)
Significant covariate on V	Weight, inotropic drugs	Weight	Weight	Weight	Weight, spironolactone	Weight	Weight
V formula	39.4 × (weight/70) × Finotrope	39.3 × (weight/70)	0.66 × weight	36.6 × (weight/70)	0.572 × (1 − 0.344 × spironolactone) × weight	0.669 × weight	Vss = 0.793 × weight + 0.01
							Vc = 0.0334 × weight
Validation method	Basic goodness-of-fit plots, Bootstrapping	Basic goodness-of-fit plots	Basic goodness-of-fit plots, Bootstrapping	Basic goodness-of-fit plots, Bootstrapping, Box-plots	Basic goodness-of-fit plots, Bootstrapping, Visual predictive check	Basic goodness-of-fit plots	Basic goodness-of-fit plots, external evaluation
Vancomycine analytical method	PETINIA on Dimension	PETINIA on Dimension	FPIA on TDx	FPIA on Cobas Integra	FPIA on TDx	FPIA on TDx	EMIT and FPIA
Serum creatinine method	Jaffé	Jaffé	Enzymatic	Jaffé	†	Jaffé	Jaffé