TABLE 2.
Population parameter estimates and pharmacokinetics dataa
| Parameter | Value |
||
|---|---|---|---|
| Median (95% CI) | MAWD (95% CI) | Range | |
| Ke1 (h−1) | 0.158 (0.104–0.272) | 0.119 (0.0.065–0.186) | 0.001–1 |
| Ke2 (h−1) | 0.465 (0.0.367–0.546) | 0.138 (0.066–0.190) | 0.001–1 |
| KCP (h−1) | 72.082 (59.067–79.618) | 13.154 (8.285–21.189) | 25–100 |
| KPC (h−1) | 11.127 (7.490–12.904) | 3.262 (1.279–4.830) | 5–20 |
| V1 (liters) | 3.712 (2.874–5.169) | 1.595 (0.948–2.934) | 1–20 |
| V2 (liters) | 0.602 (0.204–0.993) | 0.336 (0.006–0.483) | 0.001–1 |
CI, confidence interval of the estimates; MAWD, median absolute weighted deviation, used as an estimate of the variance for a nonparametric distribution; range, interval of values set before the run. In the model, Ke = Ke1 + (eGFR/94 × Ke2), where Ke is the elimination rate constant from the central compartment (per hour) and eGFR/94 is the estimated glomerular filtration rate (milliliters per minute) normalized to the population mean. KCP is the constant of transfer from the central compartment to the peripheral compartment (per hour). KPC is the constant of transfer from the peripheral compartment to the central compartment (per hour). V = V1 × (WT/74)V2, where V is the volume of the central compartment (liters) and WT/74 is the weight (kilograms) normalized to the population mean. The median (minimum to maximum) value of the unbound fraction from 214 individual observed data was 7.57% (1.61 to 49.30%). The median (minimum to maximum) value of CSF/plasma diffusion from 8 individual observed data was 14.39% (5.86 to 65.94%).