Table IV.
Comparison of Miltefosine Paediatric PBPK Model Predictions With the Clinic Trial Data
| Colombian paediatric | East Africa | ||||||
|---|---|---|---|---|---|---|---|
| Clinical trial | Simulation | Clinical trial | Simulation | ||||
| Total no. of patients | 29 | 29 × 10 trials | 21 | 21 × 10 trials | |||
| Demographic data | Female patients percentage n(%) | 41.4 | 41.4 | 24 | 24 | ||
| Ethnicity, n | Afro-Colombian & Mestizo | Sim-Paediatric | Kenya, 7 (33); Sudan, 14 (67) | Sim-Paediatric | |||
| Age (years) | 8(2–12) | 7 (2–12) | 10(7–12) | 9.5 (7–12) | |||
| Body weight (Kg), mean (range) | 26.5 (12.6–45.9) | 26.4 (9.2–63) | 24 (16–65) | 25 (10.3–54.1) | |||
| Height (cm) | 126 (92–153) | 126 (92–158) | 135 (107–153) | 135.6 (121.5–153.6) | |||
| dose | 2.5(mg/kg/day) | 2.5 (mg/kg/day) | |||||
| Patients with treatment failure percentage n (%) | 17.2 | 26.5 | 41 | 43.8 | |||
| Prediction | FE | Prediction | FE | ||||
| Plasma PK data | Cmax, (µg/mL), mean (range) | 22.7 (17.0–29.3) | 28.7 (8.1–81.2) | 1.2 | 19.9 (14.4–37.7) | 24.4 (6.4–74) | 1.2 |
| Tmax, (days), mean (range) | 27.8 (13.9–28) | 28 | 1.0 | NR | 28 | - | |
| t½ (days), mean (range) | NR | 3.7 (3.3–4.0) | - | 7.02 (4.02–8.45) | 3.21 (1.6–3.9) | 0.5 | |
| AUCd0-28 (µg⋅day/mL), mean (range) | 448 (304–583) | 685.4 (219.2–1609.6) | 1.5 | 321.9 (261.2 – 478.0) | 590.5 (173.1–1484.3) | 1.8 | |
| AUCd0-∞ (µg⋅day/mL), mean (range) | 652 (438–832) | 818.2 (228.5–2623.6) | 1.2 | 550.5 (404.1- 891.6) | 693.6 | 1.2 | |
| Intracellular PK data | Cmax, (µg/mL), mean (range) | 55.6 (19.8–382) | 56.4 (16–159.3) | 1.0 | NM | 48 (12.5–145.2) | - |
| Tmax, (days), mean (range) | 23.2 (13.0–28.0) | 28 | 1.2 | NM | 28 | - | |
| AUCd0-28 (µg⋅day/mL), mean (range) | 964 (393–4552) | 1345.4 (430.2–3159.4) | 1.3 | NM | 1159.1 (339.7–2913.5) | - | |