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Table 4 Statistical distributions selected for each pharmacodynamic parameter

From: Assessing the utility of an anti-malarial pharmacokinetic-pharmacodynamic model for aiding drug clinical development

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 = I C 50 (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)  
  1. ARS – artesunate, ART – artemether, DHA – dihydroartemisinin, LF – lumefantrine, MQ – mefloquine, PQ – piperaquine.
  2. aDrug independent parameters.
  3. 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 (μln, σln); μln and σln positive real numbers); and U – Continuous-uniform: (U (a, b); a < b; a and b real numbers).
  4. cThe mode of the triangular distribution for k max (c) was calculated from the following expression: k max = 1 / K Z × ln P R R + 1 / 48 × ln P M F , 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 k max (a/b) is calculated by evaluating the latter expression k max at a PRR decreased/increased by 50-fold (KZ remains unchanged).
  5. d I C 50 (adjusted) = I C 50 × (100 – BM / 100) × (100 / 100 - HPPB) × HWB;
  6. 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.