Table 2.
Population pharmacokinetic model development (one-compartment linear model)
| Covariate | Model | -2LL | Δ-2LL | P-value |
|---|---|---|---|---|
| 1 | Base model (No mixture) | 6 111.639 | ||
| 2-1 | ||||
| CL | ||||
| Race | M1 | 6 009.777 | −101.862 | <0.005 |
| Sex | M2 | 6 101.284 | −10.355 | <0.005 |
| Age | M3 | 6 108.711 | −2.928 | >0.05 |
| Weight | M4 | 6 111.215 | −0.424 | >0.05 |
| Smoking status | M5 | 6 101.284 | −10.355 | <0.005 |
| CM-fluoxetine | M6 | 6 084.481 | −27.158 | <0.005 |
| CM-paroxetine | M7 | 6 101.568 | −10.071 | <0.005 |
| 2-2 | ||||
| V | ||||
| Race | M8 | 6 094.077 | −17.562 | <0.005 |
| Sex | M9 | 6 100.865 | −10.774 | <0.005 |
| Age | M10 | 6 107.901 | −3.738 | >0.05 |
| Weight | M11 | 6 104.669 | −6.97 | >0.005 |
| Smoking status | M12 | 6 111.103 | −0.536 | >0.05 |
| 3-1 (mixture model on CL M13) | ||||
| CL (mixture on CL two-component) | M13 | 5 289.626 | −822.013 | <0.005 |
| CL (mixture on CL three-component) | M14 | 5 103.056 | −1008.582 | <0.005 |
| CL(RACE) | M15 | 5 128.500 | 25.444 | >0.05 |
| CL(SEX) | M16 | 5 121.475 | 18.419 | >0.05 |
| CL(AGE) | M17 | 5 146.085 | 43.029 | >0.05 |
| CL(SMOK) | M18 | 5 145.838 | 42.782 | >0.05 |
| CL(CM-PAROXETINE) | M19 | 5 145.996 | 42.94 | >0.05 |
| CL(CM-FLUOXETINE) | M20 | 5 117.367 | 14.311 | >0.05 |
| 3-2 (Mixture on CL three-component with covariates on V) | ||||
| V (Race) | M21 | 5 145.845 | 42.789 | >0.05 |
| V (Sex) | M22 | 5 146.080 | 43.024 | >0.05 |
| V (Age) | M23 | 5 143.338 | 40.282 | >0.05 |
| V (Weight) | M24 | 5 101.473 | −1.583 | >0.05 |
| 3-3 base model parent and metabolite with mixture elimination for parent (as above) | ||||
| Base model – three-component mixture on CL of parent. | M25 | 12 469.226 | ||
| CLM (age) | M26 | 12 397.024 | −72.202 | <0.005 |
CM, concomitant medication; V, volume of distribution; Δ-2LL, objective function value (OFV) from covariate model minus base model; -2LL values in 2-1 and 2-2 were compared with base model; -2LL values of M13 and M14 in 3-1 were compared with model M1; whereas values of Model 15 to Model 24 in 3-1 and 3-2 were compared with 3-1 M14; values in 3-3 was compared with 3-2 M25. The incorporation of covariates is described in Subjects and methods.