Table 3.
Parameters of the Final Olanzapine Population Pharmacokinetic Model
| Parameter (Units) | Estimate | %RSE | 95% CI | CV% |
|---|---|---|---|---|
| CL/F (L/h) | 15.5 | 2.85 | 14.6‐16.4 | … |
| Vc/F (L) | 656 | 2.23 | 627‐685 | … |
| Ka (h) | 0.861 | 5.70 | 0.765‐0.957 | … |
| ALAG (h) a | 0.782 (fixed) | … | … | … |
| Vp/F (L) | 225 | 9.42 | 183‐267 | … |
| Q/F (L/h) | 6.15 | 18.4 | 3.94‐8.36 | … |
| WT on CL/F b | 0.75 (fixed) | … | … | … |
| WT on Vc/F b | 1.0 (fixed) | … | … | … |
| Rifampin inducer effect (in the presence vs absence of rifampin) on CL/F | 1.80 | 4.45 | 1.64‐1.96 | … |
| Smoking (smokers vs nonsmokers) on CL/F | 1.30 | 3.64 | 1.21‐1.39 | … |
| Food (fed vs fasted) on F | 0.943 | 2.26 | 0.901‐0.985 | … |
| Age on Vc/F | 0.356 | 11.8 | 0.273‐0.439 | … |
| Moderate hepatic impairment (moderate hepatic impairment vs normal hepatic function) on CL/F a | 0.875 (fixed) | … | … | … |
| Severe renal impairment (severe renal impairment vs normal renal function) on CL/F | 0.801 | 5.67 | 0.712‐0.890 | … |
| Race (Black vs non‐Black) on CL/F | 1.10 | 3.22 | 1.03‐1.17 | … |
| Sex (women vs men) on CL/F | 0.862 | 3.56 | 0.802‐0.922 | … |
| Interindividual variability | ||||
| CL/F | 0.171 | 10.0 | 0.137‐0.205 | 43.2 |
| Vc/F | 0.127 | 17.5 | 0.084‐0.171 | 35.6 |
| Ka | 0.209 | 50.2 | 0.003‐0.415 | 48.2 |
| ALAG | 0.319 | 9.53 | 0.259‐0.379 | 61.3 |
| VpF | 0.223 fixed | … | … | 50.0 |
| Q/F | 0.223 fixed | … | … | 50.0 |
| Interoccasion variability in Ka | 0.630 | 14.2 | 0.455‐0.805 | 93.7 |
| Residual variability in σ2 prop | 0.0462 | 6.26 | 0.0405‐0.0519 | 21.5 |
σ2, variance of residual error quantity ε; ALAG, absorption lag time; CI, confidence interval; CL/F, apparent clearance; CV, coefficient of variation; F, bioavailability; IIV, interindividual variability; Ka, rate of absorption; Q/F, intercompartmental clearance; RSE, relative standard error; Vc/F, apparent volume of central compartment; Vp/F, apparent volume of peripheral compartment; WT, time‐changing body weight.
a
Fixed at estimate from previous stable model where effect was reliably estimated.
b
Fixed at allometric exponent.
Where estimate >0.15, CV calculated as rather than square root of .