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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.).