Table 2 Parameter estimates of the final pharmacokinetic-pharmacodynamic model

Pharmacokinetics

 Artesunate

  F (%)

100 fix

–

31.2 (29.4)

19.3–50.8

  MTT (h)

1.34 (18.8)

1.04–1.96

85.3 (24.9)

65.7–133.0

  CL_ARS/F (l/h)

1750 (8.55)

1570–2090

26.8 (44.3)

11.9–39.1

  V_ARS/F (l)

1300 (12.6)

1110–1660

74.7 (27.3)

57.8–129

  RUV (%)

73.2 (3.95)

69.3–78.7

–

–

 Dihydroartemisinin

  CL_DHA/F (l/h)

76.7 (6.99)

69.9–87.8

21.3 (30.3)

13.3–88.1

  V_DHA/F (l)

102.0 (8.95)

89.5–119.0

31.6 (40.5)

21.3–131.0

  RUV (%)

58.5 (3.34)

56.6–63.4

–

–

 Covariate effects

  ^aPARA_MTT (Log10 parasitaemia)

0.115 (8.88)

0.121–0.156

–

–

  ^aPARAmax_F

1.51 (11.9)

1.35–2.02

–

–

  ^aPARA50_F (Log10 parasitaemia)

8.32 (3.58)

8.19–9.21

–

–

 Pharmacodynamics

  K_GROWTH (48 h⁻¹)

10 fix

–

  BASE_PARA (Log₁₀)

11.0 (0.704)

10.8–11.1

4.4 (19.6)

3.13–5.78

  k_e0 (h⁻¹)

0.123 (33.1)

0.0584–0.188

–

  ^aEC₅₀ (nM)

30.4 (34.2)

13.5–46.1

–

  ^aEmax_S (h⁻¹)

0.268 (5.89)

0.242–0.295

^b49.0 (22.4)

34.3–70.1

  Emax_R (h⁻¹)

0.155 (6.08)

0.142–0.172

12.2 (45.5)

6.54–35.8

  P_{MIX, resistant} (%)

56.1 (20.9)

39.1–73.8

–

  RUV (%)

33.3 (5.91)

30.5–37.1

–