TABLE 1.

Parameter estimates for the final population PK model

	Parameter (unit)	NONMEM		Bootstrap
		Estimate	95% CI	Median	95% CI a
Fixed effect	CL (L/h)	0.0159	0.0157–0.0161	0.0159	0.0156, 0.0161
	V1 (L)	3.59	3.55, 3.63	3.59	3.55, 3.62
	V2 (L)	6.04	5.94, 6.14	6.05	5.93, 6.17
	Q (L/h)	0.0194	0.0189, 0.0199	0.0195	0.0187, 0.0202
Covariate effect
Effect of weight	WT on CL	0.561	0.512, 0.610	0.561	0.512, 0.613
	WT on V1	0.506	0.467, 0.545	0.505	0.465, 0.544
	WT on V2	0.320	0.269, 0.371	0.319	0.263, 0.374
Effect of age	Age on V2	0.207	0.139, 0.275	0.207	0.136, 0.276
Effect of race, Asian	CL	0.125	0.0903, 0.160	0.125	0.0917, 0.161
	V1	−0.044	−0.067, −0.020	−0.044	−0.067, −0.022
	V2	−0.148	−0.176, −0.120	−0.149	−0.180, −0.116
Effect of sex, male	CL	0.134	0.112, 0.156	0.135	0.111, 0.156
	V1	0.146	0.128, 0.164	0.146	0.127, 0.164
	V2	0.129	0.106, 0.152	0.129	0.106, 0.156
Effect of MMSEBL	MMSEBL on V2	0.182	0.0963, 0.268	0.183	0.0929, 0.279
IIV b	CL, % CV	21.6	21.0, 22.2	21.6	20.9, 22.2
	V1, % CV	14.8	14.2, 15.4	14.8	14.2, 15.5
	V2, % CV	17.0	16.2, 17.8	17.0	16.0, 17.9
	Weighting on residual error, % CV	34.9	33.6, 36.2	34.6	31.5, 37.7
	ρ (CL, V1)	0.378	0.352, 0.400	0.378	0.352, 0.402
	ρ (CL, V2)	−0.407	−0.500, −0.327	−0.408	−0.517, −0.317
	ρ (V1, V2)	0.392	0.360, 0.408	0.390	0.360, 0.403
Residual error	Proportional error (%)	14.8	14.6, 15.0	14.8	14.5, 15.0
	Additive error (mg/L)	0.202	0.189, 0.215	0.200	0.175, 0.227

Abbreviations: CI, confidence interval; CL, clearance; CV, coefficient of variation; IIV, interindividual variability; MMSEBL, Mini‐Mental State Examination score at baseline; NONMEM, nonlinear mixed‐effect modeling software; ρ, correlation; PK, pharmacokinetic; Q, intercompartmental clearance; V₁, central volume; V₂, peripheral volume; WT, weight.

^a Twenty‐seven runs were skipped while calculating bootstrap summaries.

^b %CV = $100\ast (\sqrt{{\exp }^{\mathrm{\omega }2}‐1})$.