Table 3.
Final population-pharmacokinetic parameters with 95% confidence interval (CI) based on sampling importance resampling
| Parameter | Estimated value (95% CI) | IIV, (%) (95% CI) | IOV, (%) (95% CI) |
|---|---|---|---|
| CL, (L/h) | 20.9 (16.8–24.7) | 42.1 (30–60) | |
| V1, (L) | 220 (187–246) | 10 Fixed | |
| Ka, (1/h) | 0.579 Fixed | 10 Fixed | 98.3 Fixed |
| Q, (L/h) | 72.0 (529–767) | 10 Fixed | |
| V2, (L) | 469 (399–579) | 10 Fixed | |
| Bmax (WBC), (pg/mL) | 2700 (1750–3835) | 27 (19–36) | |
| Kd (WBC), (pg/mL) | 0.142 (0.087–0.195) | 3 Fixed | |
| Nplasma | 137 (120–152) | 29 (22–41) | |
| F | 1 Fixed | 10 Fixed | 65 (58–84) |
| RUV | SD-PE (95% CI) |
|---|---|
| WBC | 16.7% (15.8–17.6) |
| UPC | 36.3% (33.9–40.4) |
| TPC | 31.6% (28.6–34.2) |
| Correlation RUV (WBC, UPC and TPC) | R |
|---|---|
| R (WBC, UPC) | 0.26 |
| R (WBC, TPC) | 0.51 |
| R (UPC, TPC) | 0.51 |
| Parameter | Range (minimum–maximum) |
|---|---|
| AUC (WBC), (μg h/L) | 151.2 (31.2–2525) |
| AUC (UPC), (ng h/L) | 266 (10–928) |
| T1/2 (WBC), (h) | 9.4 (6.0–31.4) |
AUC area under the curve, Bmax maximum binding capacity, IIV inter-individual variability, IOV inter-occasional variability, Cl clearance, F bioavailability, h hours, ka absorption constant rate, kd diffusion constant rate, Nplasma total plasma to unbound plasma coefficient, Q inter-compartmental clearance, R correlation coefficient, RUV residual unexplained variability, SD-PE standard deviation point estimate, T1/2 half-life, TPC total plasma concentration, UPC unbound plasma concentration, V distribution volume, WBC whole-blood concentration