Table 3.

Parameter estimates of the final population pharmacokinetic model

	Estimate	95% CIa	Shrinkage (%)
Population parameters
Clpop (L/h)	4.38	4.17–4.59
Vd,pop (L)	15.6	15.0–16.2
ka,pop (h–1)	1.99	1.76–2.27
F1pop	1.00 (fixed)
COVCl,time (h–1)	− 0.000782	− 0.00101 to − 0.000561
COVCl,age (year–1)	− 0.0125	− 0.0151 to − 0.0100
ka,Ethiopia (fold change ka,pop)	0.224	0.151–0.305
F1Ethiopia (fold change F1pop)	2.46	1.59–4.01
F1Kenya,Sudan (fold change F1pop)	1.17	1.06–1.30
Between-subject variability
Cl (CV%)	33.2	30.1–36.5	29
Vd,Eastern-Africa (CV%)	31.5	23.3–41.0	40
F1Ethiopia (CV%)	150	120.3–189.1	8
Residual variability
Proportional error India (CV%)	56.1	54.6–57.9	10
Proportional error Eastern Africa (CV%)	64.6	62.1–67.7	10

${\text{Cl}}_{\text{TV}}={\text{Cl}}_{\text{pop}}\times {\left(\frac{{\text{WT}}_{i,t}}{{\text{WT}}_{\text{med}}}\right)}^{0.75}\times e^{\text{TIME}\times {\text{COV}}_{\text{Cl,time}}}\ast \left(1+\left({\text{AGE}}_i-{\text{AGE}}_{\text{med}}\right)\times {\text{COV}}_{\text{Cl,age}}\right)$

$V_{d,\text{TV}}=V_{d,\text{pop}}\times {\left(\frac{{\text{WT}}_{i,t}}{{\text{WT}}_{\text{med}}}\right)}^{1.00}$

AGE_i individual age (years), AGE_med median population age (20 years), CI confidence interval, Cl_pop population apparent oral clearance, Cl_TV typical value apparent oral clearance, COV_Cl,age scaling factor covariate age on clearance, COV_Cl,time scaling factor covariate time on clearance, CV% percentage coefficient of variation, F1_Ethiopia proportional change of F1 in Ethiopia, F1_Kenya,Sudan proportional change of F1 in Kenya and Sudan, F1_pop population bioavailability, k_a,Ethiopia proportional change of k_a in Ethiopia, k_a,pop population absorption rate constant, SIR sampling-importance resampling, TIME time after start of treatment, V_{d,Eastern-Africa} central volume of distribution in Eastern African patients, V_d,pop population central volume of distribution, V_d,TV typical value central volume of distribution, WT_i,t individual body weight (kg) at time t, WT_med median population body weight (39 kg)

^a Obtained by SIR