TABLE 2.

Summary of pharmacokinetic (PK) parameter estimates obtained from the final apoA‐I population PK model

	Model	Nonparametric bootstrap (300 replicates)
Parameter	estimate (%RSE)	Median	95% CI (lower limit)	95% CI (upper limit)
Fixed effect
CL (L h−1)	0.11 (5.2)	0.11	0.10	0.13
Vc (L)	4.48 (2.2)	4.86	4.65	5.09
Q (L h−1)	0.25 (7.9)	0.25	0.22	0.29
Vp (L)	2.47 (6.6)	2.53	2.22	2.90
BL (mg L−1)	1219 (0.01)	1216	1196	1231
AMI on CL	0.92 (10.8)	0.87	0.72	1.08
WT on CL	1.28 (12.9)	1.25	0.73	1.65
WT on Vc	0.53 (12.2)	0.54	0.41	0.65
Total dose≥ 6 g on Vc	0.82 (2.5)	0.81	0.77	0.86
WT on BL	−0.12 (19.6)	−0.12	−0.17	−0.08
Female on BL	1.08 (1.2)	1.08	1.06	1.10
Japanese on BL	1.12 (2.3)	1.13	1.08	1.18
Study 1001 on BL	1.16 (2.3)	1.17	1.12	1.22
Random effect
IIV on CL (%)	60.9 (19.8)	64.0	48.1	79.1
IIV on Vc (%)	28.2 (18.9)	27.9	22.1	34.3
IIV on BL (%)	14.6 (14.6)	14.6	13.7	16.0
IOV on BL (%)	11.3 (4.7)	10.8	8.7	14.0
Residual error (%)
Proportional: AEGIS‐I study	7.9 (4.5)	7.9	7.3	8.5
Proportional: other studies	5.5 (3.9)	5.5	5.2	6.0
η‐shrinkage (%)
CL	45.8
Vc	36.2
BL	18.4

The functional form of the PK‐covariate relationships found in the PK model is displayed below:

$$\mathrm{CL}=0.11•{\left(\frac{\mathrm{WT}}{84}\right)}^{1.28}•{0.92}^{\mathrm{AMI}}$$

$$\mathrm{Vc}=4.84•{\left(\frac{\mathrm{WT}}{84}\right)}^{0.53}•{0.82}^{\text{Doseflag}}$$

$$\mathrm{BL}=1219•{\left(\frac{\mathrm{WT}}{84}\right)}^{-0.12}•{1.16}^{\text{Studyflag}}•{1.12}^{\mathrm{Jp}}•{1.08}^{\mathrm{Sex}}$$

where AMI = 1 for post‐AMI subjects; Doseflag = 1 for total dose ≥6 g; Studyflag = 1 for study_1001; Jp = 1 for Japanese subjects; Sex = 1 for female subjects. Those items are equal to 0 for the rest subjects. Abbreviations: AMI, acute myocardial infarction; BL, baseline apoA‐I plasma concentration; CL, systemic clearance; IIV, interindividual variability; IOV, interoccasion variability; PK, pharmacokinetic; Q, intercompartmental clearance; RSE, relative standard error; RSE%, relative standard error of the parameter estimates; Vc, volume of the central compartment; Vp, volume of the peripheral compartment; WT, weight.