Table 7. A comparison between whole-body physiologically based pharmacokinetic and the proposed methods for the pediatric dose projection.
| Drugs/age | PBPK | Weight based | Salisbury | Clearance based | ||||
|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||
| 0.75 | 0.90 | 1.0 | 0.75 | 0.90 | 1.0 | |||
| Moxifloxacin (IV), dose in mg/kg | ||||||||
| >0.25–<2 years | 9–10 | 9 | 7 | 6 | 8 | 9 | 7 | 6 |
| ≥2–<6 years | 7–8 | 8 | 7 | 6 | 8 | 11 | 9 | 8 |
| ≥6–≤14 years | 5–6 | 7 | 6 | 6 | 8 | 8 | 8 | 7 |
| Mefloquine (IV), total dose in mg | ||||||||
| 0.25–<2 years | 62.5 | 56 | 41 | 34 | 48 | 58 | 43 | 36 |
| National guidelines suggest a dose range of 32.5–62.5 mg | ||||||||
| Nilotinib (oral) | ||||||||
| 2–<6 years | 230 mg/m2 | 265 | 244 | 231 | 224 | 225 | 201 | 186 |
| 6–12 years | 230 mg/m2 | 248 | 238 | 231 | 216 | 206 | 190 | 180 |
| 12–<18 years | 230 mg/m2 | 238 | 234 | 231 | 216 | 202 | 193 | 186 |
| Radiprodil (oral)*, dose in mg/kg b.i.d, observed pediatric dose is not known. The dose was compared with PBPK dose projection. Adult dose=30 mg, adult CL=6 L/h from Johnson et al. (PBPK manuscript) | ||||||||
| 1 year | 0.1 | 0.34 | 0.26 | 0.21 | 0.30 | 0.34 | 0.26 | 0.21 |
| 6 months | 0.21 | 0.39 | 0.27 | 0.21 | 0.30 | 0.39 | 0.27 | 0.21 |
| 7 months | 0.21 | 0.37 | 0.27 | 0.21 | 0.30 | 0.37 | 0.27 | 0.21 |
| Dolutegravir (oral), total dose in mg | ||||||||
| 0–28 days | 2–5 | 5.8 | 3.8 | 2.9 | 4.0 | 4.2 | 2.6 | 1.9 |
| Oxycodone (IV), dose in mg/kg | ||||||||
| Neonates | 0.07 | 0.21 | 0.14 | 0.10 | 0.14 | 0.17 | 0.10 | 0.07 |
| Toddler (1–2 years) | 0.12 | 0.16 | 0.12 | 0.10 | 0.14 | 0.16 | 0.12 | 0.10 |
| Preschool (4–5 years) | 0.12 | 0.14 | 0.11 | 0.10 | 0.14 | 0.15 | 0.13 | 0.11 |
| School age (5–12) | 0.12 | 0.12 | 0.11 | 0.10 | 0.13 | 0.14 | 0.13 | 0.12 |
| Adolescents | 0.10 | 0.11 | 0.10 | 0.10 | 0.11 | 0.11 | 0.11 | 0.11 |
| Lorazepam (IV), dose in mg/kg | ||||||||
| Neonates (0 day old) | 0.0037 | 0.061 | 0.039 | 0.028 | 0.040 | 0.025 | 0.013 | 0.0085 |
| 1 month old | 0.0077 | 0.058 | 0.038 | 0.028 | 0.040 | 0.025 | 0.014 | 0.0091 |
| Lisinopril (oral) | ||||||||
| Infants to toddlers | 1–2.5 mg | 3.9 | 2.8 | 2.3 | 3.2 | 3.9 | 2.8 | 2.3 |
| Midazolam (IV), total dose in mg (0.1 mg/kg) in children, adult dose=5 mg/kg | ||||||||
| Preterm | 0.21 | 0.45 | 0.28 | 0.20 | 0.24 | 0.26 | 0.15 | 0.10 |
| Term | 0.28 | 0.52 | 0.33 | 0.24 | 0.29 | 0.40 | 0.24 | 0.17 |
| Remdesivir (based on body weight of 3 and 35 kg), observed dose is not known; the dose was compared with PBPK dose projection of 5 mg/kg in children (reference 86) | ||||||||
| Preterm (3 kg) | 15 | 19 | 12 | 9 | 10 | 15 | 9 | 6 |
| Young (35 kg) | 175 | 119 | 107 | 100 | 130 | 136 | 125 | 119 |
| Hydroxychloroquine, observed dose is not known; the dose was compared with PBPK dose projection of 6 mg/kg in children | ||||||||
| 5 kg | 30 | 55 | 37 | 29 | 34 | 46 | 30 | 22 |
| 15 kg | 90 | 126 | 100 | 86 | 120 | 126 | 100 | 86 |
| 35 kg | 210 | 238 | 214 | 200 | 260 | 271 | 251 | 238 |
*
Radiprodil: PBPK projected dose of 0.21 mg/kg/b.i.d. was based at 60% RO response. PBPK: Physiologically based pharmacokinetic, RO: Receptor occupancy, IV: Intravenous