Table 4.
Cmax and AUC0−∞ predicted using population pharmacokinetic model in CYP2C19 non-PM obese children and adolescents, following the FDA-approved weight-tiered dosing, total body weight-based dosing, and lean body weight-based dosing, and published reported values in non-obese peers and adults.
| Non-obese | Adults [34] |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| Children (age 6–11 yrs) n=18 |
Adolescents (age 12–17 yrs) n=19 |
Children (age 6–11 yrs) n=12 [34] |
Adolescents (age 12–16 yrs) n=11 [33] |
||||||
| Dosing regimen | FDA-approved weight-tiered dosing | LBW-based dosing | TBW-based dosing | FDA-approved weight-tiered dosing | LBW-based dosing | TBW-based dosing | 40 mg | FDA-approved weight-tiered dosing | FDA-approved dosing |
| Dose | 20 mg (weight 15–39 kg) |
1.2 mg/kg | 1.0 mg/kg | 20 mg (weight 15–39 kg) |
1.2 mg/kg | 1.0 mg/kg | 40 mg | 20 mg (weight 15–39 kg) |
40 mg |
| Cmax (mcg/mL) | 3.69 ±
1.08 (2.02–5.45) |
4.47 ±
1.12 (2.34–6.59) |
5.60 ±
1.08 (3.55–7.46) |
2.58 ±
0.61 (1.70–3.41) |
4.37 ±
0.76 (3.14–6.35) |
4.98 ±
1.09 (3.39–6.75) |
1.8 | 2.2 ± 1.4 | 2.5 |
| AUC0−∞ (mcg*h/mL) |
5.94 ±
1.97 (3.00–8.89) |
7.28 ±
2.56 (3.12–13.39) |
9.15 ±
2.92 (4.39–15.13) |
4.73 ±
1.93 (2.35–11.03) |
7.95 ±
2.68 (4.70–16.55) |
9.20 ±
3.89 (4.70–22.07) |
6.9 | 4.3 ± 3.1 | 4.8 (1.4–13.3) |
A maximum dose of 80 mg was used in simulation; pharmacokinetic parameters are given as geometric mean or mean ± standard deviation (range), when available. AUC, area under the curve; Cmax, maximum serum concentration; FDA, US Food and Drug Administration; LBW, lean body weight; PM, CYP2C19 poor metabolizer; TBW, total body weight.