. Author manuscript; available in PMC: 2016 Feb 11.

Published in final edited form as: Pharm Res. 2014 May 2;31(10):2643–2654. doi: 10.1007/s11095-014-1361-z

Table II.

Population Parameter Estimates of the Final System-Specific Pharmacology Model with the System-Specific Function for GFR Mediated Clearance and Drug-Specific Information on Gentamicin, Tobramycin and Vancomycin

Parameter	Final pharmacokinetic covariate model (CV%)
Fixed effects
System specific parameters: ${C L}_{GFR} = {C L}_{Drug} \times {(\frac{B W}{4 k g})}^{BDE} BDE = L 1 \times {B W}^{M}$ (Eq. 9)
L1	2.23 (6.23)
M	−0.065 (−12.1)
Drug specific parameters:
CLgenta _{4 kg} (L/h)	0.21 (2.01)
CLtobra _{4 kg} (L/h)	0.28 (2.47)
CL vanco _{4 kg} (L/h)	0.39 (2.72)
V1genta _{4 kg} (L)	1.45 (2.94)
V1tobra _{4 kg} (L)	1.90 (1.99)
V1vanco _{4 kg} (L)	2.22 (2.63)
V1genta=V_{4 kg}×(BW/4 kg)^k2 (Eq. 8)
k2	0.759 (4.35)
V1tobra=V_{4 kg}×(BW/4 kg)^k3 (Eq. 8)
k3	0.735 (2.56)
V1vanco=V_4kg×(BW/4 kg)^k4 (Eq. 8)
k4	1 FIX
Qgenta=CLgenta	–
Qtobra=CLtobra	–
Qvanco=CLvanco	–
V2genta=V1genta	–
V2tobra=V1tobra	–
V2vanco=V1vanco	–
Interindividual variability
ω² on CLgenta	0.143 (12.5)
ω² on CLtobra	0.158 (16.5)
ω² on CLvanco	0.171 (10)
Residual variability
σ² (proportional)	0.0886 (5.21)
σ² (additive) (mg/L)	0.0494 (22.7)

CL clearance, CL_{4 kg} clearance for a full term neonate of 4 kg, Q intercompartmental clearance, V1 volume of distribution of the central compartment, V2 volume of distribution of the peripheral compartment, BW bodyweight (g), L1 coefficient of the bodyweight dependent exponent function, M bodyweight dependent exponent, k2 the exponent of bodyweight on V1 of gentamicin, k3 the exponent of bodyweight on V1 of tobramycin, k4 the exponent of bodyweight on V1 of vancomycin