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

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

Population pharmacokinetics analysis Bootstrap evaluation
Parameter Estimate RSE (%)a BSV (%)b RSE (%)a Estimate CI95% c BSV (%)b CI95% c
F1 (%) 100 fixed   56 16 100 fixed   53 29 to 70
θday F1 − 0.29 54    − 0.33 − 0.57 to 0.05   
θage F1 − 0.68 19    − 0.68 − 0.91 to − 0.31   
CL (L/h) 146 20    139 91 to 202   
VC (L) 139 23    131 78 to 199   
Ka (h−1) 3.2 fixed     3.2 fixed    
CLM d (L/h) 11 15    11 8 to 15   
V dM (L) 11 20 60 29 10 7 to 15 49 16 to 75
σprop,AS (CV%) 79 8    78 65 to 92   
σprop,DHA (CV%) 60 9    60 48 to 69   
Corrprop (%) 44 36    43 40 to 64   
σadd,AS (nmol/mL) 0.0023 3    0.0023 0.0022 to 0.0025   
σadd,DHA (nmol/mL) 0.0042 13    0.0041 0.0035 to 0.0049   
  1. F1, AS relative bioavailability; CL, AS clearance; VC, AS central volume of distribution; Ka, first-order absorption rate constant; CLM, DHA clearance; VM, DHA volume of distribution; σprop, exponential residual error; σadd, additive residual error; corrprop, correlation between the proportional error components; θage F1, age effect on F1 expressed as (1 + θage F1(AGE-MAGE)/MAGE) with MAGE = 2.6 years; median AGE value in the study population; θday F1, day effect on F1 expressed as (1 + θday F1Q1) with Q1 = 0 for the first treatment day; 1 for subsequent therapy days
  2. 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
  3. bBetween-subject variability
  4. c95% confidence interval (CI)
  5. 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: CLM,ind = CLM*(BW/MBW)0.75 and VM,ind = VM*BW/MBW, respectively, with BW patient’s body weight