Table 4.

Melphalan population pharmacokinetic parameter estimates using the final covariate population pharmacokinetic model (model development dataset)

Parameter	Meaning	Population mean (95% CI)	Variability in estimation
			SE	%RSE
θ1	Constant in CL model	Fixed to zero
θ2	Constant in V model	1.12 (0.11, 2.13)	0.506	45%
θ3	Constant in k12 model	1.70 (1.16, 2.24)	0.270	16%
θ4	Constant in k21 model	1.84 (1.39, 2.29)	0.224	12%
θ5	Coefficient for WT in CL	0.34 (0.26, 0.42)	0.0405	12%
θ6	Coefficient for CPT in CL	−3.17 (−4.62, −1.72)	0.725	23%
θ7	Coefficient for GFR in CL	0.0377 (0.021, 0.054)	0.00838	22%
θ8	Coefficient for WT in V	0.178 (0.120, 0.236)	0.0288	16%
IIVCL	Interindividual variability in CL	27.3% (21, 32)	0.0143	32%
IIVV	Interindividual variability in V	33.8% (20, 43)	0.0366	32%
IIVk12	Interindividual variability in k12	52.2% (30, 68)	0.0924	34%
IIVk21	Interindividual variability in k21	61.7% (28, 83)	0.151	40%
σ	Residual variability*
	Proportional (%CV)	9.3% (7, 11)	0.00189	22%
	Additive (mg l−1)	0.00731 (−0.004, 0.019)	0.00565	77%
Objective function	−177.345

Structural models:

where WT = weight (kg), CPT = prior carboplatin therapy (0 = no, 1 = yes), GFR = glomerular filtration rate (ml min⁻¹ 1.73 m⁻²). IIV, Interindividual variability in the pharmacokinetic parameters, expressed as percentage coefficient of variation (%CV); variability in estimation: SE, standard error; RSE, relative standard error, calculated as standard error/population estimate and expressed as a percentage.

^*Proportional component of residual variability was expressed as %CV, while the additive component was expressed as standard deviation. 95% CI, Lower and upper limits of the 95% confidence interval, calculated as θ ± 2 SE.