TABLE 2

Mean PPQ PK parameters for the two- and three-compartment model calibrationsa

ParameterValue for following calibration (reference):
2a (20)2b (22)2c (21)3a (23)3b (14)3c (24)
Study populationCambodianBurmese and KarenCambodianThaiBurkinabeSudanese
Study sizeAdults and children (n = 60)Adults (n = 87) and children (n = 11)Adults (n = 38)Pregnant (n = 24) and nonpregnant (n = 24) womenChildren (n = 236)Pregnant (n = 24) and nonpregnant (n = 24) women
D (mg/kg)2.9/22.9 at 0 and 24 h, 1.9/15.2 at 48 h7/55 split into 3 or 4 doses1.7/13.6 at 0, 6, 24, and 32 h2.1/17 at 0, 24, and 48 h12.4/8.8 at 0, 24, and 48 h2.3/18.1 at 0, 6, 24, and 32 h
Typical BW (kg)424847481853
CL (liters/day)108 · BW0.75 (1.01)1,584 · [1 + 0.0262 · (BW − 48)] (0.42)939.1d (0.71)10.0 (0.38)12.1g (0.45)
ka (day−1)11.2b (2.17)17.2 (1.68)1.99 (1.08)3.5e (1.08)1.99f (1.08)1.99f (1.08)
k (day−1)1.4 (0.78)
Q1 (liters/kg/day)69.7 (1.01)65.5 (0.85)106.8d (1.02)17.5 (5.32)10.8g (0.94)
Q2 (liters/kg/day)52.0d (0.70)14.4 (0.66)119.5g (0.51)
k12 (day−1)4.6 (0.57)
k21 (day−1)0.1 (1.31)
Vc (liters/kg)346.0 (0.93)8,660 · [1 + 0.0273 · (BW − 48)]/BW (1.01)14.5 (0.46)57.6d (0.86)13.7 (2.16)34.3 (0.53)
Vp1 (liters/kg)443.0 (1.70)500.0 (0.50)559.5c92.5 (1.21)14.1 (2.15)300.0 (0.60)
Vp2 (liters/kg)654.2 (0.65)185.6 (0.51)141.9 (0.81)
  • a BW, body weight of the typical patient in the original study; D, dose of DHA and PPQ administered to the typical patient in the original study; CL, clearance; ka, absorption rate; k, elimination rate (k = CL/Vc); Q1, intercompartmental clearance between the central compartment and peripheral compartment 1; Q2, intercompartmental clearance between the central compartment and peripheral compartment 2; k12, rate of transfer from the central compartment to the peripheral compartment (k12 = Q1/Vc); k12, rate of transfer from the peripheral compartment to the central compartment (k21 = Q1/Vp1); Vc, central volume of distribution; Vp1, volume of distribution in peripheral compartment 1; Vp2, volume of distribution in peripheral compartment 2. The CV of each value is shown in parentheses. −, no data or not applicable.

  • b The value was 50% lower than that in the original study (20).

  • c Calculated from the steady-state volume of distribution (Vss), i.e., Vp1 = VssVc, and reported only for completeness (Vp1 is not required for calculations, and the CV was not given in the original study).

  • d CL, Q1, Q2, and Vc were 35, 50, 10, and 10%, respectively, lower than in the original study.

  • e Value taken from reference 21 and 75% higher than that in the original study.

  • f Value taken from reference 21.

  • g CL, Q1, and Q2 were 40, 50, and 25% lower, respectively, than in the original study.