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. 2021 Oct 26;11(1):7–19. doi: 10.1002/psp4.12728

TABLE 2.

Parameter estimates for the final population PK‐PD model

Parameter (unit) NONMEM Bootstrap
Estimate 95% CI Median 95% CI a
Fixed effect BL 1.40 1.39, 1.41 1.40 1.39, 1.41
K out (1/h) 8.51 E−05 7.59E−5, 9.42E−5 8.40E−05 7.55E−5, 9.35E−5
Emax 0.702 0.606, 0.797 0.697 0.616, 0.820
EC50 (mg/L) 46.4 33.8, 59.0 45.2 35.2, 61.0
Covariate effect
Effect of weight WT on K out 0.414 0.155, 0.673 0.403 0.132, 0.645
Effect of age BL 0.101 0.0326, 0.169 0.0954 0.0282, 0.177
Effect of ApoE ε4 Noncarrier on BL −0.0404 −0.0547, −0.0260 −0.0402 −0.0571, −0.0246
Carrier (2 copies) on BL 0.00896 −0.0096, 0.0275 0.00923 −0.00987, −0.0270
Effect of MMSEBL MMSEBL on BL −0.186 −0.256, −0.116 −0.187 −0.263, −0.116
IIV b K out, % CV 44.2 29.8, 54.9 43.1 31.3, 55.8
Emax, % CV 25.3 15.8, 32.0 24.0 13.1, 32.6
BL, % CV 12.8 12.2, 13.3 12.8 12.1, 13.5
EC50, % CV 84.1 72.6, 94.2 84.9 69.9, 100
ρ (K out, Emax) −0.872 −3.17, −0.245 −0.863 −3.71, −0.232
ρ (Emax, BL) 0.439 0.157, 0.593 0.378 0.107, 0.601
ρ (BL, EC50) −0.406 −0.772, −0.151 −0.457 −0.854, −0.143
Residual error Proportional error (%) 4.04 3.89, 4.18 4.03 3.86, 4.20

ApoE, apolipoprotein E; BL, baseline SUVR; CV, coefficient of variation; EC50, aducanumab exposure that produces 50% of the maximum attainable stimulation; Emax, maximum fold change in the elimination of SUVR as a response to aducanumab exposure; K in, zero‐order rate for production of SUVR; K out, first‐order rate of elimination of SUVR; MMSEBL, Mini‐Mental State Examination score at baseline; NONMEM, nonlinear mixed‐effect modeling software; ρ, correlation; PD, pharmacodynamic; PK, pharmacokinetic; WT, weight.

a

One hundred twenty‐two runs were skipped while calculating bootstrap summaries.

b

%CV = 100(expω21).