Table 4.
Covariate screen: Objective function changes after adding individual covariates into the base population pharmacokinetic models for total and unbound melphalan
| Model for total melphalan | Model for unbound melphalan | ||||
|---|---|---|---|---|---|
| Covariate | Covariate equations | ΔOBV | P value* | ΔOBV | P value* |
| CLcr (ml min−1 /70 kg−1) | CL =θ1+θ2× (CLcr/88) V1 =θ3 | −34 | <0.01 | −26 | <0.01 |
| CLcr (ml min−1) | CL =θ1+θ2× CLcr/97 V1 =θ3 | −37 | <0.01 | −28 | <0.01 |
| HCT | CL =θ1+θ2× (HCT/34) V1 =θ3 | −8 | <0.01 | −12 | <0.01 |
| TBW | CL =θ1+θ2× (TBW/70)0.75V1 =θ3× (TBW/70) | −4 | <0.05 | −15 | <0.01 |
| TBW | CL =θ1× (TBW/70)0.75V1 =θ2× (TBW/70) | +3 | NS | −11 | <0.01 |
| FFM | CL =θ1+θ2× (FFM/53)0.75V1 =θ3× (FFM/53) | −12 | <0.01 | −12 | <0.01 |
| FFM | CL =θ1× (FFM/53)0.75V1 =θ2× (FFM/53) | −3 | NS | −4 | <0.05 |
| BSA | CL =θ1+θ2× (BSA/1.9) V1 =θ3× (BSA/1.9) | −6 | <0.05 | −10 | <0.01 |
| BSA | CL =θ1× (BSA/1.9) V1 =θ2× (BSA/1.9) | −3 | NS | −6 | <0.05 |
| Age | CL =θ1+θ2× (Age/57) V1 =θ3 | +9 | NS | +5 | NS |
| Sex | CL =θ1+θ2× (1−sex) V1 =θ3 | −1 | NS | 0 | NS |
| ALB | CL =θ1× (ALB/37) V1 =θ2× (ALB/37) | +28 | NS | +50 | NS |
| TPR | CL =θ1× (TPR/71) V1 =θ2× (TPR/71) | −1 | NS | +9 | NS |
*
Significance in the change in Objective function value (ΔOBV) was assessed using the likelihood ratio test, ALB, albumin; BSA, body surface area; CLcr, estimated creatinine clearance; FFM, fat free mass; HCT, haematocrit; NS, Not significant; TBW, total body weight; TPR, total protein.