TABLE 1.
Parameter estimates and bootstrap results of the final pharmacokinetic model of AST-001.
| Parameter | Estimate | RSE (%) | Bootstrap median (95% CI) a |
|---|---|---|---|
| Population parameters | |||
| V1/F (L) | 68.4 | 6.7 | 67.8 (59.0–75.5) |
| CL/F (L/h) | 22.9 | 5.8 | 22.8 (20.9–24.9) |
| V2/F (L) | 196 | 11.6 | 198.8 (165.5–242.7) |
| Q/F (L/h) | 16.4 | 7.3 | 16.6 (14.7–18.8) |
| D1 (h) | 1.26 | 7.6 | 1.27 (1.13–1.54) |
| R1 (g/h) | 0.287 | 6.2 | 0.284 (0.259–0.311) |
| Inter-individual variability b | |||
| V1/F | 29.0 | 13.1 | 27.9 (20.6–33.8) |
| CL/F | 22.2 | 23.9 | 21.1 (12.0–29.2) |
| D1 | 38.0 | 13.6 | 37.6 (26.7–47.8) |
| R1 | 18.0 | 23.6 | 17.4 (9.9–24.0) |
| Covariance between V1/F and CL/F c | 0.0483 | 41.8 | 0.0444 (0.0173–0.0758) |
| Residual Error | |||
| Proportional residual error d | 0.183 | 7.5 | 0.182 (0.160–0.204) |
RSE, relative standard error; CI, confidence interval; V1/F, apparent volume of distribution in the central compartment; CL/F, apparent clearance; V2/F, apparent volume of distribution in the peripheral compartment; Q/F, apparent inter-compartmental clearance between the central and peripheral compartments; D1, duration of zero-order absorption; R1, rate of endogenous production of AST-001.
a
Results of bootstrap resampling for 1000 replicates.
b
Inter-individual variability is presented as coefficient of variation (%).
c
Untransformed estimates of covariance between V1/F and CL/F.
d
Proportional residual error is presented as coefficient of variation.