Table 2.
Pharmacokinetic parameter estimates for the final population model.
| Final Model | Bootstrap (n=1,000) | |||||
|---|---|---|---|---|---|---|
| Model parametera | Symbol | Point Estimate | RSE (%) | 2.5% | Median | 97.5% |
| V1 (L/kg) | θV1 | 0.879 | 11.2 | 0.607 | 0.786 | 0.969 |
| CL (L/h/kg0.75) | θCL | 0.115 | 5.5 | 0.108 | 0.119 | 0.131 |
| V2 (xV1) | θV2 | 0.542 | 32.7 | 0.452 | 0.737 | 1.250 |
| Q (L/h/kg0.75) | θQ | 1.450 | 50.8 | 1.100 | 2.520 | 4.981 |
| Exponent for (Age/4.7 yr) on CL | θCL-AGEY | 0.133 | 33.2 | 0.024 | 0.094 | 0.188 |
| Between-Subject Variability (CV%)b | ||||||
| ηV1 | ω2V1 | 47% | 37% | 50% | 60% | 75% |
| ηCL | ω2CL | 40% | 18% | 75% | 81% | 86% |
| ηV2 | ω2V2 | 57% | 91% | 17% | 48% | 85% |
| Residual variance (WSV) (CV%)c | ||||||
| ERR, STUDY=1 | σ2 STUDY1 | 33% | 66% | 31% | 42% | 61% |
| ERR, STUDY=2 | σ2 STUDY2 | 22% | 82% | 18% | 29% | 51% |
| Weighting Exponent | θPOWER | 1.290 | 13.9 | 0.956 | 1.170 | 1.340 |
V1: central compartment volume; CL: clearance; V2: peripheral compartment volume; Q: intercompartmental clearance; RSE: relative standard error of estimate.
V1 (L)=0.879*WT; CL (L/h)=0.115*WT0.75*(AGE/4.7)0.133; V2 (L)=0.542*V1; Q (L/h) = 1.45*WT0.75.
The covariance (cov) between etas for V1 and CL (covV1,CL), V1 and V2 (covV1,V2), and CL and V2 (covCL,V2) were 0.163, −0.159, and 0.0348, respectively.
The relationship between observations and individual predictions was described according to the following relationship: Y=IPRED+ERR(1)*(θSTUDY1*(2-STUDY)+θSTUDY2*(STUDY-1))*(IPRED**θPOWER), where IPRED represents the individual prediction; θSTUDY1 and θSTUDY2 are the residual error terms for the Status 1 and Status 2 trials, respectively; ERR(1) was fixed to unity; and the individual predictions were raised to a power exponent denoted as θPOWER.