Table 2.
Parameter estimates of the final population PK model
| Parameters | Final estimate (RSE%) | 95% CIs |
|---|---|---|
| CL, L/h/65 kg | 0.0138 (5.7) | 0.012–0.015 |
| Weight for CL | 0.594 (10.2) | 0.475–0.713 |
| ALB for CL | −1.07 (9.6) | −1.272 to −0.868 |
| ESR for CL | 0.101 (27.7) | 0.046–0.156 |
| nCD64 for CL | 0.168 (16) | 0.115–0.221 |
| ATI for CL | 0.134 (9.6) | 0.109–0.159 |
| V1, L/65kg | 2.97 (4.5) | 2.709–3.231 |
| Weight for V1 | 0.55 (20.2) | 0.332–0.768 |
| Q, L/h/65 kg | 0.0095 FIXED | – |
| Weight for Q | 1 FIXED | – |
| V2, L/65 kg | 2.84 (3.6) | 2.642–3.038 |
| Weight for V2 | 0.586 FIXED | – |
| Interindividual variability (%CV) | Shrinkage (%) | |
| ω (CL) | 25.1 (9) | 6.3 |
| Residual error (SD) | Shrinkage (%) | |
| σadd | 0.435 (1.5) | 5.2 |
The covariate analysis for CL included age, body weight, body mass index, sex, race, clinical activity wPCDAI, and laboratory measurements including ESR, serum ALB, CRP, nCD64, hemoglobin, platelet count, fecal calprotectin, and ATI concentrations. The equation for the final model is CLind = CLpop × WT/65)0.594 × (ALB/3.5)−1.07 × (ESR/9)0.101 × (nCD64/4.6)0.168 × (ATI/22)0.134. V1ind = V1pop × (WT/65) 0.55 . Qind = Qpop × (WT/65). V2ind = V2pop × (WT/65)0.586. Residual error is additive error for log transformed concentrations.
ALB, albumin; ATI, antibody to infliximab; CI, confidence interval; CL, clearance; CV, coefficient of variation; ESR, erythrocyte sedimentation rate; Ind, individual; nCD64, neutrophil CD64 activity ratio; pop, population; PK, pharmacokinetic; Q, inter-compartmental clearance; RSE, relative standard error; V1, central compartment volume of distribution; V2, peripheral compartment volume of distribution; wPCDAI, weighted pediatric CD activity index.