. 2016 Jun 30;82(3):793–805. doi: 10.1111/bcp.13016

Table 1.

Overview of amikacin population pharmacokinetic (PK) model parameter estimates in neonates reported in the literature.

	Botha et al. 1998 8	Allegaert et al. 2006 7	Allegaert et al. 2008 13	Sherwin et al. 2009 3	De Cock et al. 2012 6
Patients (n)	53	205	715	80	874
Body weight (kg), range	n.r.	0.45‐1.98	0.39‐4.78	0.45‐4.43	0.39‐4.78
Gestational age (w), range	Mean 35.1 (SD 3.6)	24‐30	n.r.	24‐41	24‐43
Postnatal age (d)	3.1 (3.1)	0‐2	0‐28	3‐64	1‐30
Postconceptional age (d)	n.r.	168‐210	n.r.	n.r.	n.r.
Postmenstrual age (d)	n.r.	n.r.	168‐301	172‐308	n.r.
Structural model	1 compartment	1 compartment	1 compartment	1 compartment	2 compartment
PK estimates
Θ_CL (L/h)	0.031	0.486†	1.49§	0.23	0.0493¶
Θ_V1 (L)	0.316	40.2‡	31.7‡	0.957	0.833**
Θ_Q (L/h)	‐	‐	‐	‐	0.415
Θ_V2 (L)	‐	‐	‐	‐	0.833
Final covariate model	CL = Θ_CL WT^ΘCL‐WT Θ_CL‐G	CL = [Θ_CL (WT/70)^0.75] EXP [Θ_CL‐SLPCL SLPCL (PCA‐24) Θ_CL‐FSNAID FNSAID]	CL = Θ_CL (WT/70)^0.75 (1 + Θ_CL‐SLPCL SLPCL (PMA‐40)) (Θ_CL‐RF RF) (Θ_{CL‐Fventilation} Fventilation) (Θ_CL‐VENT VENT) (Θ_{CL‐Finotrope} Finotrope) (Θ_CL‐INO INO) (Θ_CL‐Fiugr Fiugr) (Θ_CL‐SGA SGA)	CL = Θ_CL (WT/2)^ΘCL‐WT (PMA/40)^ΘCL‐PMA	CL = Θ_CL (bWT/median)^ΘCL‐bWT+ (1 + Θ_CL‐PNA (PNA/median) + (Θ_CL‐IBU IBU)
	V = Θ_V1 WT^ΘV‐WT	V = Θ_V1 (WT/70)¹	V = Θ_V (WT/70)¹ (1 + Θ_V‐SLPV SLPV PNA) (Θ_{V‐Finotrope} Finotrope) (Θ_V‐INO INO) (Θ_{V‐Fventilation} Fventilation) (Θ_V‐VENT VENT)	V = Θ_V1 (WT/2)^ΘV‐WT	V1 = Θ_V1 (WT/median)^ΘV‐WT
					V2 = V1
					Q = Θ_Q
Covariate pharmacokinetic estimates	Θ_CL‐WT = 1.45; Θ_CL‐G = 1.28*; Θ_V‐WT = 1.44	Θ_CL‐WT = 0.75(fix); Θ_CL‐SLPCL = 0.11; Θ_CL‐FNSAID = 0.788; Θ_V‐WT = 1(fix)	Θ_CL‐WT = 0.75(fix); Θ_CL‐SLPCL = 0.032; Θ_{CL‐Fventilation} = 0.977; Θ_{CL‐Finotrope} = 0.945; Θ_CL‐Fiugr = 0.872; Θ_V‐WT = 1(fix); Θ_V‐SLPV = 0.005; Θ_{V‐Finotrope} = 1.09; Θ_{V‐Fventilation} = 1.08	Θ_CL‐WT = 0.691; Θ_CL‐PMA = 3.23; Θ_V‐WT = 0.89	Θ_CL‐bWT = 1.34; Θ_CL‐PNA = 0.213; Θ_CL‐IBU = 0.838; Θ_V‐WT = 0.919

θ‐CLG = 1 for boys;

^†

expressed as l h⁻¹ per 70 kg at 24 weeks of postconceptional age, without NSAID;

^‡

expressed as l per 70 kg;

^§

expressed as l h⁻¹ per 70 kg at 40 weeks of postmenstrual age, and RF = 1;

^¶

for a typical individual with bWT of 1750 g and PNA of 2 days;

^**

for a typical individual with a WT of 1760 g.

n.r.: non reported; bWT: birthweight; G: Gender; SLPCL: factor relating PCA to developmental changes in CL; FNSAID: scaling factor for those premature neonates given a NSAID; RF: Renal function parameter standardized to creatinine clearance of L/h/70Kg in a 40‐year‐old person with serum creatinine of 85.947 µmol l⁻¹, calculated as CPR(creatinine production rate) = 516 EXP(Kage ((PMA‐30)weeks/52‐40)) µmol h⁻¹ (Kage = 0.00344) and CLcr = CPR/Serum Creatinine L/hCL; Finotrope, Fventilation and Fiugr are scaling factors applied for the use of inotropes (INO), positive pressure artificial ventilation (VENT) or intrauterine growth retardation (SGA); INO, VENT and SGA have a value of 1 if present and 0 if absent