TABLE 3.
Parameter estimates and bootstrap medians (95% confidence intervals) for final pharmacodynamic models of nafamostat in patient and ECMO models.
| Parameter | Patient model | ECMO model | ||||
|---|---|---|---|---|---|---|
| Estimate | RSE (%) | Bootstrap median (95% CI) | Estimate | RSE (%) | Bootstrap median (95% CI) | |
| Structural model | ||||||
| θImax | 0.355 | 21.8 | 0.356 (0.233–0.608) | 0.436 | 9.25 | 0.436 (0.359–0.518) |
| θIC50 (μg/L) | 350 a | 581 a | ||||
| θKin (s/h) | 47.5 | 32.5 | 49.7 (6.13–158) | 50.6 | 26.9 | 49.3 (31.6–107) |
| θBase (s) | 34.5 | 4.47 | 34.5 (31.9–37.8) | 33.0 | 4.43 | 32.9 (30.3–36.1) |
| Interindividual variability | ||||||
| ωImax (%) | 50.7 a | 27.3 a | ||||
| ωEC50 (%) | 70.6 a | 0.000 a | ||||
| ωKin (%) | 105 | 23.3 b | 88.5 (0.000–161) | 75.8 | ||
| ωBase (%) | 20.7 | 13.2 b | 20.3 (13.5–24.9) | 21.2 | 16.4 b | 20.2 (12.9–26.8) |
| Residual unexplained variability | ||||||
| σAdditive error (s) | 2.83 | 18.6 | 2.76 (1.82–3.91) | 3.43 | 16.9 | 3.34 (2.03–4.41) |
RSE, relative standard error; RSE (%) = (standard error/parameter estimate) × 100; Imax, maximum inhibitory effect; IC50, effective concentration of drug that causes 50% Imax; Kin, turnover rate; Base, baseline aPTT, level.
a
fixed.
b
RSE (%) for standard deviation = (standard error/variance estimate) × 100/2.