TABLE 2.
Sequential covariate model developmenta
| Model | Hypothesis | OFV | ΔOFV | Basis of model | % IIV for CL (% RSE) |
|---|---|---|---|---|---|
| 0 | Base model | 631.909 | Base model | 23.6 (26.4) | |
| 1 | TVCL = θ1 + [θ2 · (CLCR/110)] | 612.237 | −19.672 | Base model | 18.5 (36.2) |
| 2 | TVCL = θ1 · (age/30)θ2 | 614.46 | −17.449 | Base model | 19.5 (44.1) |
| 3 | TVCL = θ1 · (SCR/0.78)θ2 | 618.743 | −13.166 | Base model | 21.3 (33.5) |
| 4 | TVV1 = θ1 + θ2 · sex | 612.284 | −19.625 | Base model | 24.9 (26.4) |
| 5 | TVV1 = θ1 · (WT/63)θ2 | 613.321 | −18.588 | Base model | 25.5 (25.3) |
| 6 | TVQ = θ1 · (SCR/0.78)θ2 | 607.963 | −23.946 | Base model | 22.5 (29.1) |
| 7 | TVQ = θ1 + θ2 · sex | 617.805 | −14.104 | Base model | 24.5 (26.5) |
| 8 | TVQ = θ1 · (WT/63)θ2 | 620.045 | −11.834 | Base model | 24.5 (27.0) |
| 9 | TVCL = θ1 + [θ2 · (CLCR/110)], TVV1 = θ3 + θ4 · sex | 592.092 | −20.145 | 1 | 19.2 (40.2) |
| 10 | TVCL = θ1 + [θ2 · (CLCR/110)], TVV1 = θ3 · (WT/63)θ4 | 593.972 | −18.265 | 1 | 20 (37.8) |
a
OFV, objective function value; ΔOFV, change in the objective function value; IIV, interindividual variability; RSE, relative standard error; TV, typical value; CL, clearance; θi, typical value of the PK parameter; Q, intercompartmental clearance; V1, central compartment volume; SCR, serum creatinine concentration; CLCR, creatinine clearance; WT, weight.