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Table 4 Final population parameter estimates of artemether, lumefantrine, mefloquine and piperaquine and estimates from the bootstrap evaluation in 200 replicates

From: Population pharmacokinetics of mefloquine, piperaquine and artemether-lumefantrine in Cambodian and Tanzanian malaria patients

Population analysis Bootstrap evaluation
Parameter Estimate S.E.a IIVb S.E.c Mean of 200 S.E. 95% C.I.d
Artemether        
CL [L/h/kg] 24.7 × BW0.75 10% 44% 17% 24.4 × BW0.75 10% 19–29
θ INH −0.3 45%    −0.27 60% 0.5–1.1
V C [L/kg] 129 20%    133 26% 88–232
V M [L] Fixed to V C       
ka [h-1] 0.27 11% 119% 11% 0.27 14% 0.21–0.35
k23 [h-1] 5.86 21% 68% 9% 5.83 25% 3.6–9.7
CL met [L/h] 419 30%    440 42% 213–927
σ C (CV%) 74% 9% c    73% 11% c 59%–86%
σ M (CV%) 119% 11% c    116% 9% c 88%–149%
Lumefantrine        
CL [L/h/kg] 0.84 × BW θ BWCL 28% 38% 14% 0.87 × BW θ BWCL 24% 0.51-1.37
θ BWCL 0.52 19%    0.51 14% 0.36-0.65
V C [L/kg] 59.9 × BW θ BWCL 28% 33% 11% 59.5 × BW θ BWCL 24% 35.1–91.9
θ BWVC 0.35 28%    0.34 19% 0.19-0.45
V M [L] Fixed to V C       
k a [h-1] 0.54 31%    0.48 43% 0.11–0.88
F0 [mg] 2.53 14% 103% 14% 2.45 15% 1.58–3.28
k23 [h-1] 3.7 × 10-4 12% 38% 15% 3.7 × 10-4 9% (3.0–4.4) × 10-4
CL met [L/h] 4.8 10%    4.6 13% 3.4–5.7
σ C (CV%) 60% 9% c    61% 31% 55%–77%
σ M [μmolL-1] 0.013 4% c    0.013 45% 0.010–0.016
Mefloquine        
CL [L/h/kg] 0.10 × BW0.75 5% 12% 88% 0.10 × BW0.75 5% (0.09–0.11)
V C [L/kg] 8.93 × BW 6% 19% 96% 9.01 × BW 6% (8.04–10.20)
ka [h-1] 0.15 14%    0.15 14% 0.12–0.19
F0 [mg] 33.1 56% 175% 48% 31.0 43% 11.8–48.1
σ C [μmolL-1] 43% 6% c    43% 6% c 0.14–0.22
Piperaquine        
CL [L/h/kg] 4.50 × BW0.75 13% 45% 61% 4.26 × BW0.75 22% (3.24–5.76)
V C [L/kg] 346 × BW 12% 65% 48% 347 × BW 13% (260–432)
Q [L/h] 122 13%    126 13% 86–158
V P [L] 18,600 22% 50% 77% 20,053 37% 8,778–28,422
ka [h-1] 0.93 28%    1.00 34% 0.35–1.52
F0 [mg] 123 18%    125 18% 75–171
σ C [μmolL-1] 41% 10% c    41% 6% c 0.14–0.21
  1. Abbreviations: CL clearance, BW body weight, θ INH inhibitors effect (CYP3A4 and/or CYP2C19) on CL expressed as (1- θ INH × INH), V C central volume of distribution, Q inter-compartment clearance, V M volume of distribution of the metabolite, V P peripheral volume of distribution, k a first-order absorption rate constant, F0 residual amount from the previous treatment, k23 metabolism rate constant, CLmet metabolite clearance, σ C exponential residual error for the central compartment, σ M : exponential residual error for the metabolite compartment.
  2. a Standard error (S.E.) of the estimate θ i defined as S.E estimate/estimate, expressed as a percentage.
  3. b Inter-individual variability.
  4. c Standard error (S.E.) of the coefficient of variation defined as √S.E estimate/estimate, expressed as a percentage.
  5. d 95% confidence interval (C.I.).