Table 3.

Population pharmacokinetic parameters of the final models using unbound and total concentrations of imatinib for the prediction of C_u (Model A) or C_tot (Model B)(simultaneous analysis)

Total PK Parameters	Total PK parameters		Unbound PK parameters	Unbound PK parameters
	Model A: Cu = f (Ctot)*			Model B: Ctot = f (Cu)†
	Estimate	SE (%)‡		Estimate	SE (%)§
CLtot (l h−1)	13.8	5	CLu (l h−1)	386	6
Vd,tot (l)	409	17	Vd,u (l)	9 580	20
katot (h−1)	0.80	73	kau (h−1)	0.93	70
Kd (ng ml−1)	319	2	Kd (ng ml−1)	316	3
L	11 700¶	–	L	11 700¶	–
Interindividual variability			Interindividual variability
ωCL,tot (CV%)**	27	53§	ωCLu (CV%)**	25	66§
ωVd,tot (CV%)**	48	75§	ωVd,u (CV%)**	64	81§
Correlation CL-Vd	0.59		Correlation CL-Vd	0.65
Residual variability			Residual variability
σ Ctot (CV%)††	14	40§	σ Ctot (CV%)††	15	41%§
σ Cu (CV%)††	17	41§	σ Cu (CV%)††	14	41%§
Correlation Cu-Ctot	0.72		Correlation Cu-Ctot	0.66

^*In this model, total PK parameters CL_tot, V_d,tot and ka_tot are estimated and C_u are predicted using:

(see text).

^†in this model, total unbound PK parameters are estimated CL_u, V_d,u and ka_u, and C_tot are predicted using:

(see text).

^‡SE, standard error of the estimates, expressed as CV%.

^§SE, standard error of the variance components, taken as square (SE_estimate/estimate), expressed as a percentage.

^¶Fixed value that represent the scaling factor that accounts for the difference in concentration unit between C_tot (ng ml⁻¹) and total protein concentration AGP (g l⁻¹), assuming a one-to-one molar binding ratio.

^**Estimates of variability expressed as coefficient of variation (CV%).

^††Residual variability of the plasma concentration, expressed as CV%.