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

Table 3 Final population parameter estimates of mefloquine 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	1 FIX		28	15	1 FIX		27	18 to 34
CL (L/h)^d	0.45	7	39	17	0.45	0.39 to 0.51	38	24 to 51
V_C (L)^d	95	7			92	66 to 106
K_a (h⁻¹) DAY = 1	0.17	17	91	12	0.16	0.10 to 0.23	87	64 to 110
K_a (h⁻¹) DAY > 1	0.40	22	91	12	0.38	0.22 to 0.64	87	64 to 110
θ_{AGE Ka}	− 0.67	18			− 0.66	− 0.91 to − 0.29
Q (L/h)^d	0.35	28			0.35	0.24 to 1.30
V_P(L)^d	60	9			61	51 to 82
σ_prop (CV %)	21	13			20	14 to 26

F1, bioavailability; CL, clearance; V_C, central volume of distribution; K_a, first-order absorption rate constant; Q, intercompartmental clearance; V_P, peripheral volume of distribution; σ_prop, exponential residual error; θ_{AGE Ka}, effect of AGE on K_a expressed as (1 + θ_{AGE Ka} (AGE–AGE)/MAGE) with MAGE = 2.6 years; median AGE value in the study population
^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). Individual clearance, peripheral clearance and volumes of distribution are obtained by the equations: CL_M,ind = CL*(BW/MBW)^0.75, Q_M,ind = Q*(BW/MBW)^0.75, V_C,ind = V_C * BW/MBW, and V_P,ind = V_P * BW/MBW, respectively, with BW patient’s body weight

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