. Author manuscript; available in PMC: 2015 May 15.

Published in final edited form as: Clin Cancer Res. 2014 Mar 17;20(10):2783–2792. doi: 10.1158/1078-0432.CCR-13-2364

Table 2.

Final Population Pharmacokinetic Parameter Median Estimates and Confidence Interval from 1,000 Bootstrap Replicates of Original Dataset

Parameter/Covariate Relationship	Median Estimate (95% CI)	Inter-Individual Variability, % CV ^a (95% CI)	Inter-Occasion Variability, % CV ^b (95% CI)
CL (mL/day/kg) = θ_CL × e^{BMI% × θ_BMI%,CL}
θ_CL	5.16 (4.36 – 5.74)	18.4 % (8.4 – 33.9 %)	18.2 % (13.3 – 22.6 %)
θ_BMI%,CL	-0.004 (-0.006 – -0.002)	18.4 % (8.4 – 33.9 %)	18.2 % (13.3 – 22.6 %)

V_normalized (L/kg) = θ_V × e^{BMI% × θ_BMI%,V}
θ_V	62.7 (57.5 – 69.0)	13.2 % (9.0 – 17.6 %)	4.7 % (1.6 – 7.4 %)
θ_BMI%,V	-0.005 (-0.006 – -0.003)	13.2 % (9.0 – 17.6 %)	4.7 % (1.6 – 7.4 %)

k₁₂ (hr^-1)	0.222 (0.187 – 0.268)	25.0 % (12.7 – 37.3 %)	---

k₂₁ (hr^-1)	0.335 (0.250 – 0.418)	49.8 % (15.1 – 87.7 %)	---

Residual variability
Proportional	0.014 (0.004 – 0.018)	---	---
Additive	0.003 (-0.003 – 0.010)	---	---

CL: clearance, V_normalized : volume of central compartment, k₁₂ and k₂₁: inter-compartmental rate constants,

$\sqrt{ω^{2}} \times 100 %$ and

$\sqrt{ø^{2}} \times 100 %$ (both from equation 1), BMI%: body mass index percentile