Population pharmacokinetics and pharmacodynamics of the artesunate–mefloquine fixed dose combination for the treatment of uncomplicated falciparum malaria in African children

Table 2 Final population parameter estimates of artesunate and dihydroartemisinin with their bootstrap evaluations in 2000 replicates

Population pharmacokinetics analysis					Bootstrap evaluation
Parameter	Estimate	RSE (%)^a	BSV (%)^b	RSE (%)^a	Estimate	CI_95% ^c	BSV (%)^b	CI_95% ^c
F1 (%)	100 fixed		56	16	100 fixed		53	29 to 70
θ_{day F1}	− 0.29	54			− 0.33	− 0.57 to 0.05
θ_{age F1}	− 0.68	19			− 0.68	− 0.91 to − 0.31
CL (L/h)	146	20			139	91 to 202
V_C (L)	139	23			131	78 to 199
K_a (h⁻¹)	3.2 fixed				3.2 fixed
CL_M ^d (L/h)	11	15			11	8 to 15
V ^d_M (L)	11	20	60	29	10	7 to 15	49	16 to 75
σ_prop,AS (CV%)	79	8			78	65 to 92
σ_prop,DHA (CV%)	60	9			60	48 to 69
Corr_prop (%)	44	36			43	40 to 64
σ_add,AS (nmol/mL)	0.0023	3			0.0023	0.0022 to 0.0025
σ_add,DHA (nmol/mL)	0.0042	13			0.0041	0.0035 to 0.0049

F1, AS relative bioavailability; CL, AS clearance; V_C, AS central volume of distribution; K_a, first-order absorption rate constant; CL_M, DHA clearance; V_M, DHA volume of distribution; σ_prop, exponential residual error; σ_add, additive residual error; corr_prop, correlation between the proportional error components; θ_{age F1}, age effect on F1 expressed as (1 + θ_{age F1}(AGE-MAGE)/MAGE) with MAGE = 2.6 years; median AGE value in the study population; θ_{day F1}, day effect on F1 expressed as (1 + θ_{day F1}Q1) with Q1 = 0 for the first treatment day; 1 for subsequent therapy days
^aRelative standard error (RSE) of the estimate defined as SE estimate/estimate, expressed as a percentage, with SE estimate retrieved directly from the NONMEM output file
^bBetween-subject variability
^c95% confidence interval (CI)
^dPharmacokinetic parameter of a patient of 12.2 kg, the median population body weight (MBW). DHA individual clearance, and volume of distribution are obtained by the equations: CL_M,ind = CLM*(BW/MBW)^0.75 and V_M,ind = V_M*BW/MBW, respectively, with BW patient’s body weight

ISSN: 1475-2875