|
Parameter
|
Drug
|
Distributionb
|
Additional details
|
|---|
|
μ
IPL
a
|
DU(4, 16)
| | |
|
σ
IPL
a
|
DU(2, 8)
| | |
|
PMF
a
|
TRI(8, 12, 10)
| | |
|
k
max
|
ARS/DHA
|
TRI(0.26, 0.47, 0.37)c
|
PRR = 105.28; KZ = 38
|
|
ART
|
TRI(0.12, 0.33, 0.22)c
|
PRR = 102.9; KZ = 38
|
|
LF
|
TRI(0.18, 0.54, 0.36)c
|
PRR = 103; KZ = 22
|
|
MQ
|
TRI(0.11, 0.46, 0.28)c
|
PRR = 102.25; KZ = 22
|
|
PQ
|
TRI(0.33, 0.65, 0.49)c
|
PRR = 104.6; KZ = 24
|
|
γ
|
ARS/DHA
|
lnN(1.31, 0.65)
| |
| |
ART
|
lnN(1.53, 0.31)
| |
| |
LF
|
lnN (0.81, 0.58)
| |
| |
MQ
|
lnN (0.97, 0.54)
| |
| |
PQ
|
lnN (1.35, 0.66)
| |
|
EC50 (ng/mL)
|
ARS/DHA
|
U(1.44, 532.05)
|
a = (adjusted)(ng/mL)b,d; b = 0.5×Cmax (ng/mL)b,d
|
| |
ART
|
U(4.38, 46.20)
| |
| |
LF
|
U(1.75, 2331.60)
| |
| |
MQ
|
U(20.48, 1087.22)
| |
| |
PQ
|
U(11.56, 94.19)
| |
- ARS – artesunate, ART – artemether, DHA – dihydroartemisinin, LF – lumefantrine, MQ – mefloquine, PQ – piperaquine.
- aDrug independent parameters.
- bDU – Discrete-uniform (DU (a, b); a < b; a and b positive integers); TRI – Triangular (TRI (a, b, c); a < c < b; a, b and c real numbers); ln N – Log-normal (lnN (μ ln, σ ln); μ ln and σ ln positive real numbers); and U – Continuous-uniform: (U (a, b); a < b; a and b real numbers).
- cThe mode of the triangular distribution for (c) was calculated from the following expression:, where PRR is the parasite reduction ratio for the drug in the corresponding row; KZ is the length of the killing zone in hours for each drug in the corresponding row; PMF in this expression equals 10 parasites / 48 h. The lower /upper limit of the triangular distribution for (a/b) is calculated by evaluating the latter expression at a PRR decreased/increased by 50-fold (KZ remains unchanged).
- d (adjusted) = × (100 – BM / 100) × (100 / 100 - HPPB) × HWB;
- BM – binding media; HPPB – human plasma protein binding; HWB – human whole blood to plasma ratio. IC50 (adjusted) values for each drug are given in Table 5 and Cmax is the peak plasma concentration of a drug after administration.
