Table 6.

Population pharmacokinetic model development (two-compartment with nonlinear elimination)

Covariate	Model	−2LL	Δ-2LL	P-value
1	Base model	17 137.900
2–1
Vm
CYP2D6	M1	16 977.144	−160.76	<0.005
Wt	M2	17 079.98	−57.92	<0.005
Age	M3	17 143.06	5.155	>0.05
Race	M4	17 133.65	−4.25	<0.05
Sex	M5	17 070.42	−67.48	<0.005
2–2
V2
CYP2D6	M6	17 071.83	−66.07	<0.005
Wt	M7	17 068.262	−69.64	<0.005
Age	M8	17 134.346	−3.55	>0.05
Race	M9	17 142.224	4.32	>0.05
Sex	M10	17 080.828	−57.07	<0.005
3–1
Vm, V2
Vm(CYP2D6, Wt)	M11	16 876.32	−100.82	<0.005
Vm(CYP2D6), V2(Wt)	M12	16 900.59	−76.55	<0.005
Vm(CYP2D6), V2(sex)	M13	16 892.90	−84.24	<0.005
Vm(CYP2D6, race)	M14	16 977.165	0.021	>0.05
3–2
Vm and V2
Vm(CYP2D6), V2(sex, Wt)	M15	16 861.53	−31.37	<0.005
Vm(CYP2D6, Wt), V2(sex)	M16	16 830.24	−62.66	<0.005

Wt, Weight; V₂, volume of distribution of central compartment;Δ-2LL was objective function value (OFV) from covariate model minus base model; −2LL values in 2–1 and 2–2 were compared with base model; −2LL values in 3–1 were compared with model M1; while values in 3–2 were compared with 3–1 M13 and M11. The incorporation of covariates is described in Subjects and methods.