Table 1 Parameter estimates of the nonlinear mixed effects model

From: Towards clinically relevant dose ratios for Cabamiquine and Pyronaridine combination using P. falciparum field isolate data

Parameter

Estimate (CI95%)

Fixed effect parameters

N0 [-]

909a

kgrowth [h−1]

0.015 (0.0082–0.0237)

Emax,cabamiquine [h−1]

0.629b

EC50,cabamiquine,t=0 [nM]

0.799 (0.33–1.03)

hcabamiquine [-]

20c

kadapt [nM−1 h−1]

0.0316 (0.027–0.035)

MAXadapt [-]

6.38 (2.46–7.74)

Emax,Pyr [h−1]

0.629b

EC50,Pyr [nM]

28.3 (20.9–42.8)

hPyr [-]

2.42 (1.44–2.59)

Baseline [-]

115 (86–214)

Interparasite variability

ω N0 [%CV]

53.1a

ω kgrowth [%CV]

73.8 (48.3–139)

ω EC50,cabamiquine,t=0 [%CV]

40.6 (5.9–74.0)

ω MAXadapt [%CV]

88.4 (38.3–131)

ω EC50,Pyr [%CV]

51.4 (26.1–78.2)

ω Baseline [%CV]

64.8 (33.6–103)

Residual error [%]

25.0 (24.1–25.3)

  1. N0 assay signal at initiation of the experiment, kgrowth growth rate, Emax maximum killing rate, EC50 concentration stimulating 50% of Emax, h steepness of the concentration-effect relationship, kadapt second-order delay rate for cabamiquine adaptive resistance development, MAXadapt maximum fractional change of the EC50 of cabamiquine, Baseline baseline readout (minimum assay signal), Prop. σ residual error of the individually predicted parasite time course vs. observations, RSE relative standard error of the parameter estimates.
  2. aFixed to experimentally obtained values.
  3. bFixed to the final estimate obtained in monotherapy.
  4. cFixed to “high” value leading to on-off effect.
  5. Parameter uncertainty was determined by log-likelihood profiling and 95% confidence intervals (CI95%) are given in brackets after each estimate for nonfixed parameters.
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