TABLE 5.
Population PK parameter estimates and post hoc secondary PK parameters from the final population PK model of ethambutol in children with TBMa
| Parameter | Population estimateb
(% RSE) |
95% CIc | % CV for IIVb
(% RSEc) |
95% CI for IIVc |
Plasmad |
|---|---|---|---|---|---|
| Primary PK parameters | |||||
| F | 1 (fixed) | 20.1 (14.2) | 14.3–25.7 | ||
| CL/F (liters/h) | 28.2 (4.68) | 25.7–30.8 | |||
| Vc/F (liters) | 98.6 (11.0) | 79.1–122 | 51.1 (10.7) | 39.7–63.6 | |
| MTT (h) | 1.8 (7.15) | 1.56–2.05 | 18.4 (21.3) | 8.60–25.5 | |
| MAT50 (mo) | 3.99 (36.0) | 1.60–7.20 | |||
| HILL | 1 (fixed) | ||||
| Q/F (liters/h) | 16.9 (12.2) | 12.9–20.9 | |||
| Vp/F (liters) | 153 (16.0) | 108–203 | 96.3 (14.2) | 63.2–134 | |
| σPlasma | 0.197 (4.45) | 0.166–0.236 | |||
| Secondary PK parameters at steady state | |||||
| AUC0–24 (mg×h/liter) | 8.18 (4.60–17.8) | ||||
| Cmax (mg/liter) | 1.26 (0.656–2.54) | ||||
| Tmax (h) | 2.59 (1.91–3.65) | ||||
| t1/2 (h) | 12.7 (3.92–21.4) | ||||
Abbreviations: F, relative bioavailability; CL/F, oral elimination clearance; Vc/F, volume of distribution of the central compartment; MTT, mean transit absorption time; MAT50, postmenstrual age at which clearance is 50% of the mature clearance; HILL, Hill coefficient for maturation clearance; Q/F, intercompartmental clearance; Vp/F, volume of distribution of peripheral compartment; IIV, interindividual variability; σ, variance of the residual variability, incorporated as an additive error on the logarithmic scale; AUC0–24, area under the concentration-time curve from 0 to 24 h; Cmax, peak concentration; Tmax, time to reach peak concentration; t1/2, terminal elimination half-life.
Computed population mean parameter estimates from NONMEM. Parameter estimates are scaled to typical patient at 10.9 kg and 3 years.
Assessed by sampling importance resampling (SIR).
Median (range).