TABLE 2.
Mean PPQ PK parameters for the two- and three-compartment model calibrationsa
| Parameter | Value for following calibration (reference): |
|||||
|---|---|---|---|---|---|---|
| 2a (20) | 2b (22) | 2c (21) | 3a (23) | 3b (14) | 3c (24) | |
| Study population | Cambodian | Burmese and Karen | Cambodian | Thai | Burkinabe | Sudanese |
| Study size | Adults and children (n = 60) | Adults (n = 87) and children (n = 11) | Adults (n = 38) | Pregnant (n = 24) and nonpregnant (n = 24) women | Children (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 h | 7/55 split into 3 or 4 doses | 1.7/13.6 at 0, 6, 24, and 32 h | 2.1/17 at 0, 24, and 48 h | 12.4/8.8 at 0, 24, and 48 h | 2.3/18.1 at 0, 6, 24, and 32 h |
| Typical BW (kg) | 42 | 48 | 47 | 48 | 18 | 53 |
| 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) | 559.5c | 92.5 (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) |
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.
The value was 50% lower than that in the original study (20).
Calculated from the steady-state volume of distribution (Vss), i.e., Vp1 = Vss − Vc, and reported only for completeness (Vp1 is not required for calculations, and the CV was not given in the original study).
CL, Q1, Q2, and Vc were 35, 50, 10, and 10%, respectively, lower than in the original study.
Value taken from reference 21 and 75% higher than that in the original study.
Value taken from reference 21.
CL, Q1, and Q2 were 40, 50, and 25% lower, respectively, than in the original study.