Table III.
Pharmacokinetic Parameter Estimates
| Parameters | Units | Mean estimate | Bootstrapped estimate (95% CI) | Shrinkage (%) |
|---|---|---|---|---|
| Nonspecific linear clearance (CL)a | L/day | 0.214 | 0.213 (0.191, 0.243) | |
| Central volume of distribution (Vc)a | L | 4.27 | 4.2 (3.4, 5.38) | |
| Intercompartmental clearance (Q) | L/day | 3.34 | 3.25 (1.41, 6.79) | |
| Peripheral volume (Vp) | L | 2.73 | 2.75 (2.2, 3.18) | |
| Absorption rate (ka) | 1/day | 0.432 | 0.428 (0.346, 0.519) | |
| Bioavailability (F) | % | 74 | 74 (66, 85) | |
| Receptor production rate (ksyn) | ng/mL/day | 51.9 | 53 (40.6, 65.4) | |
| Receptor degradation rate (kdeg) | 1/day | 0.22 | 0.222 (0.144, 0.427) | |
| Binding affinity (Kss) | ng/mL | 18.8 | 18.1 (10.6, 30.6) | |
| Internalization rate (kint) | 1/day | 0.0345 | 0.0347 (0.0251, 0.0442) | |
| BSV in CL | %CV | 25.1 | 25 (21, 29.6) | 4.3 |
| BSV in Vc | %CV | 43.8 | 43.8 (35.3, 53) | 5.6 |
| BSV in ka | %CV | 59.5 | 58.8 (45.6, 73.3) | 7.9 |
| BSV in kint | %CV | 42.3 | 42.1 (33.5, 51.7) | 6.8 |
| Covariance between ηCL and ηka | - | −0.0731 | −0.0719 (−0.127, –0.0371) | |
| Covariance between ηCL and ηkint | - | 0.0682 | 0.0664 (0.0396, 0.101) | |
| Residual variability | %CV | 17.9 | 17.6 (15.9, 19.7) | 10.7 |
95% CI = 95% confidence interval from 1000 bootstrapped runs of the final model
aMean CL and Vc estimates at 70 kg; individual body weight effect on CL and Vc were estimated as Individual CL = 0.214 (weight/70)0.75 L/day and Individual Vc = 4.27 (weight/70) L
BSV Between-subject variability expressed as %CV, CV Approximates coefficient of variation