Table 2.
Estimates of population pharmacokinetic parameters of the final model
| Parameter | Final model | Bootstrap | |||
|---|---|---|---|---|---|
| Mean | RSE (%) | Shrinkage (%) | Median | 95% CI | |
| Remdesivir | |||||
| CL (L/h) | 105 | 17.8 | 100 | 69.3–154 | |
| V (L) | 121 | 23.7 | 111 | 45.9–195.5 | |
| GS-441524 | |||||
| CL/fm (L/h) | 15.9 | 8.39 | 16.0 | 13.2–19.6 | |
| V/fm (L) | 429 | 11.4 | 429 | 353–512 | |
| Age effect on V | –1.15 | 33.7 | –1.18 | – 2.82 to – 0.51 | |
| eGFR effect on CL | 1.12 | 0.02 | 1.23 | 0.78–1.89 | |
| Between subject variability (%) | |||||
| Remdesivir CL | 53.1 | 29.5 | 10.0 | 45.4 | 9.03–77.7 |
| Remdesivir V | 61.4 | 31.2 | 12.8 | 60.2 | 14.6–122 |
| GS-441524 CL/fm | 36.8 | 17.7 | 6.91 | 34.4 | 20.1–50.1 |
| GS-441524 V/fm | 46.0 | 22.1 | –5.52 | 40.4 | 18.9–67.5 |
| Error model parameter | |||||
| Remdesivir additive residual (µM) | 0.014 | 38.1 | 0.016 | 0.0008–0.039 | |
| Remdesivir proportional error | 0.62 | 17.2 | 0.61 | 0.44–0.74 | |
| GS-441524 proportional error | 0.16 | 7.06 | 0.16 | 0.11–0.20 | |
CL, clearance; CI, confidence interval; fm, fraction of remdesivir metabolized to GS-441524; RSE, relative standard error; V, volume of distribution