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Table 1 Evaluation of elementary designsa for population pharmacokinetic studies of adults with moderately severe malaria receiving a single dose of 120 mg intravenous artesunate

From: Towards optimal design of anti-malarial pharmacokinetic studies

Number of patients

Number of samples per patient

Sampling times

Expected precisionb of PK parameter estimates (initial valuesc: Vd = 38 L, CL = 37 L.hr-1)

Expected precisionb of inter-patient variability estimates (initial values: ωVd = 0.5, ωCL = 0.5)

Expected precisionb of residual variability estimate (initial value: σε = 200 ng.mL-1)

Efficiencyd (%)

20

10

{0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6}

11.5, 11.4

33.5, 33.1

5.6

100 (criterion = 13.7)

40

5

{0.25, 0.75, 1, 2, 4}

8.2, 8.2

24.2, 24.3

6.5

157

50

4

{0.25, 0.75, 2, 4}

7.4, 7.6

21.8, 22.9

7.1

177

10

10

{0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6}

8.8, 8.9

25.8, 26.6

6.2

143

25

4

{0.25, 0.75, 2, 4}

    
  1. a – total number of blood samples constrained to be 200;
  2. b – expected precision expressed as 100 × standard error/estimate;
  3. c – Batty KT et al [30]; ω – sd of inter-patient variability (lognormal distribution);
  4. d – Relative comparison of criterion of sampling design to criterion of rich design of 20 patients (expressed as a percentage). The criterion is the determinant of the population Fisher information matrix raised to the power of one over the number of parameters to be estimated (for this example there are 5 parameters: Vd, CL, ωVd, ωCL, σε)