Table 2.
Structural and covariate parameter estimates for the ‘full’ population pharmacokinetic model after removal of component studies.
| Parameter Estimates (ratios of parameter estimates [n =1] studies/[n =5] studies) | ||||||
|---|---|---|---|---|---|---|
| Parameter | None | Study I | Study II | Study III | Study IV | Study V |
| CL/F (l h−1) | 59.0 (1.00) | 58.0 (0.98) | 58.1 (0.98) | 58.1 (0.98) | 61.1 (1.04) | 60.2 (1.02) |
| V/F (l) | 309 (1.00) | 322 (1.04) | 305 (0.99) | 295 (0.95) | 319 (1.03) | 310 (1.00) |
| ka (h−1) | 2.56 (1.00) | 2.73 (1.07) | 2.67 (1.04) | 2.56 (1.00) | 2.50 (0.98) | 2.40 (0.94) |
| Age (% change in CL/F | 3.6 (1.00) | 1.0 (0.27) | 3.4 (0.95) | 3.5 (0.96) | 5.0 (1.38) | 5.5 (1.52) |
| per 10 years) | ||||||
| AST (% change in CL/F | 6.2 (1.00) | 5.9 (0.95) | 5.3 (0.85) | 4.2 (1.16) | 8.0 (1.29) | 3.9 (0.59) |
| per 10 IU l−1) | ||||||
| CYP3A4 (θ*CL/F) | 0.88 (1.00) | 0.89 (1.01) | 0.90 (1.02) | 0.85 (0.97) | 0.89 (1.01) | 0.89 (1.01) |
| ‘Noncardioselective’ | 0.84 (1.00) | 0.81 (0.96) | 0.85 (1.01) | 0.83 (0.99) | 0.77 (0.92) | 0.98 (1.16) |
| β-blockers (θ*CL/F) | ||||||
| Weight (% change in | 5.8 (1.00) | 6.6 (1.13) | 5.7 (0.97) | 4.1 (0.7) | 7.0 (1.21) | 7.0 (1.19) |
| V/F per 10 kg) | ||||||
| Frel (200 mg vs≤100 mg) | 0.42 (1.00) | 0.44 (1.06) | 0.42 (0.99) | 0.40 (0.95) | NA | 0.42 (1.00) |
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.