Table 5.
Population parameter estimates for the final population pharmacokinetic model.
| Parameter | Estimate |
|---|---|
| CL/F (l h−1) for typical patient* | 58.5±1.40† |
| Age (% change in CL/F per 10 years) | 3.65±1.90† |
| AST (% change in CL/F per 10 IU l−1) | 6.25±2.17† |
| CYP3A4 potential inhibitor co-administration (θ*CL/F) | 0.862±0.0509† |
| V/F (l) for typical patient (87 kg) | 310±6.92† |
| Weight (% change in V/F per 10 kg) | 6.13±1.42† |
| ka (h−1) | 2.60±0.176† |
| Frel (200 mg vs≤100 mg) | 0.408±0.0779† |
| ωCL/F | 29±20%‡ |
| ωV/F | 20±50%‡ |
| ωka | 210±25%‡ |
| ωFrel | 34±11%‡ |
| σ | 47.6±11.5%§ |
CL/F=apparent clearance; V/F=volume of distribution; ka =first-order absorption constant; AST=aspartate transaminase; θ=multiplicative factor for population typical value; Frel =relative bioavailability
*
58 years old, AST 24 IU l−1, not receiving CYP3A4 potential inhibitor
†
mean±standard error of the estimate
‡
mean±relative standard error of the variance
§
coefficient of variation±standard error of estimate ka =this value is associated with meal consumption within 2 h predose, at all other times input rate is equivalent to an instantaneous bolus administration.