Table 2.

Pharmacokinetic and pharmacodynamic parameters.

Parameter	Value (%RSE, 95% CI)	Interindividual variability, % (%RSE, 95% CI)
Pharmacokinetic parameters
N (subjects/PK observations)	280/4573
Clearance (L/d)a	867 (10.2%, 727–1064)	27.1 (15.1%, 22.0–31.0)
ϴ Post menstrual age EC50a (weeks)	96 (15.4%, 73–130)	–
Volume of central compartment (L)	592 (10.1%, 484–717)	32.8 (56.3%, 11.8–48.5)
Intercompartmental clearance 1 (L/d)	511 (12.4%, 401–645)	–
Volume of peripheral compartment 1 (L)	7240 (8.2%, 6210–8440)	–
Intercompartmental clearance 2 (L/d)	671 (16.8%, 461–934)	–
Volume of peripheral compartment 2 (L)	1060 (18.2%, 731–1510)	–
Absorption transit time (d)b	0.045 (9.1%, 0.034–0.048)	43.2 (42.2%, 22.4–60.1)
ϴ Capillary to venous conversionc	0.922	–
Proportional error	44.6% (1.7%, 43.0%–46.0%)	–
Relative bioavailability (F)b	1
ϴ Weight for age z-scored	0.113 (18.9%, 0.061–0.137)	–
ϴ Self-administered DPd	0.397 (7.8%, 0.344–0.465)	–
ϴ Between occasion variability	66.9% (5.9%, 62.3%–71.3%)
Pharmacodynamic parameters
N (subjects/observations)	280/326
Baseline hazard/1000 (per day)e	0.402 (17.2%, 0.268–0.536)	69.6 (66.1, 43.3–146)
Season adjustment
ϴ Transmission period 2015	1.29 (33.9%, 0.65–2.40)	–
ϴ Transmission period 2016	5.20 (16.1%, 3.92–7.09)
ϴ Transmission  period 2017	7.83 (16.7%, 5.75–10.96)
ϴ PPQ EC50 (ng/mL)	6.00 (14.4%, 4.25–7.58)	–
ϴ PPQ γ	3.13 (24.3%, 1.96–4.89)

Confidence intervals obtained by bootstrap (n = 1000).

^aCL = ϴ_CL *${\left(\frac{\mathrm{Weight}}{8.6\mathrm{kg}}\right)}^{0.75}$*$\left(\frac{\mathrm{Post}\mathrm{menstrual}\mathrm{age}}{\theta \mathrm{Post}\mathrm{menstrual}\mathrm{age}\mathrm{EC}50+\mathrm{Post}\mathrm{menstrual}\mathrm{age}}\right)$.

^bPre-specified absorption compartments.

^cln([PPQ]_capillary) = ϴ _slope*ln([PPQ]_venous).

^dF = 1* ϴ_{Self-administered DP} *(1 + ϴ_WAZ*(WAZ−(−0.5)))*e^{ϴ Between occasion variability}, WAZ weight for age z-score.

^eSurvival function: ϴ_Baseline/1000* ϴ_{Transmission  period}*$\frac{{\left[\mathrm{PPQ}\right]}^{\gamma }}{\theta {\mathrm{EC50}}^{\gamma }+{\left[\mathrm{PPQ}\right]}^{\gamma }}$.