TABLE 3.

Population PD parameters and bootstrap CIs for the final PK/PD models for plasma Aβ42/40 ratio and p‐tau181

Parameter	NONMEM		Bootstrap
	Estimate	%RSE	Median (95% CI)
Aβ42/40 ratio
PD parameters
Baseline plasma Aβ42/40 ratio	0.0842	4.28	0.0843 (0.0834–0.0852)
K out (1/year)	0.367	1.97	0.368 (0.255–0.521)
Slope (1/μg/ml)	0.00155	9.32	0.00155 (0.00110–0.00213)
Interindividual variability
Baseline (CV%)	6.78	16.1	6.73 (4.58–8.76)
Slope (CV%)	44.1	11.1	44.3 (21.4–58.9)
Residual variability
Proportional (CV%)	6.41	2.82	6.42 (6.03–6.82)
p‐tau181
PD parameters
Baseline plasma p‐tau181	4.06	1.61	4.06 (3.97–4.14)
K out (1/year)	0.468	20.7	0.502 (0.183–0.934)
Slope (1/μg/ml)	0.00313	15.6	0.00328 (0.00178–0.00596)
Covariate effects
Weight ~ baseline (exponent)	−0.300	24.2	−0.304 (−0.439 – −0.211)
Interindividual variability
Baseline (CV%)	35.1	5.63	35.1 (33.0–37.4)
Slope (SD)	0.00151	50.2	0.00162 (0.000662–0.00280)
Residual variability
Proportional (CV%)	19.4	2.39	19.4 (18.3–20.6)

Abbreviations: %RSE = percent relative standard error of the estimate = SE/parameter estimate × 100; CI = confidence interval; CV% = Square root of variance × 100; K _out = rate constant of degradation; PD, pharmacodynamic; PK, pharmacokinetic.

p‐tau181: $\text{Baseline}=0.00313\bullet {\left(\frac{\mathrm{BW}}{72.2}\right)}^{-0.300}$.

BW = body weight.

Aβ42/40 ratio ‐ Eta shrinkage (%): ETA_Baseline = 11.9%, ETA_Slope = 63.1%.

p‐tau181 ‐ Eta shrinkage (%): ETA_Baseline = 4.65%, ETA_Slope = 68.4%.