TABLE 1.
Population pharmacokinetic parameters for artemether and dihydroartemisinin in pediatric patients with uncomplicated falciparum malaria during a 3-day treatment with six weight-based doses of artemether and lumefantrine (Coartem)
| Parameter | Estimate (95% CI)a | IIV, % CV (95% CI)a | Parameter description |
|---|---|---|---|
| ka (per h) | 1 (fixed) | NEb | Absorption rate |
| CL/FARM (liters/h/kg) | θ1 × [1 + θ2 × (occ − 1)] | 41 (37-50) | Oral clearance |
| θ1 | 2.6 (1.5-2.6) | NE | Typical value of CL/FARM |
| θ2 | 0.57 (0.39-0.75) | NE | Fractional change in CL/FARM with dose |
| Vc/FARM (liters/kg) | 5.2 (3.5-7.1) | NE | Oral volume of distribution of the central compartment |
| QARM (liters/kg) | 1.4 (1.1-1.8) | NE | Intercompartment clearance |
| Vp/FARM (liters/kg) | 41.4 (29.0-58.1) | NE | Oral volume of distribution of the peripheral compartment |
| CL/FDHA (liters/h/kg) | 6.8 (5.8-8.0) | 47 (35-57) | Oral metabolite clearance |
| V/FDHA (liters/kg) | 3.7 (2.3-8.7) | NE | Oral metabolite volume of distribution |
| σprop ARM (%) | 61 (54-67) | Proportional residual error | |
| σadd ARM (nM) | 2 (fixed) | Additive residual error | |
| σprop DHA (%) | 82 (73-90) | Proportional residual error | |
| σadd DHA (nM) | 3 (fixed) | Additive residual error |
a
95% CI from 1,000 nonparametric bootstrap data sets.
b
NE, not estimated.