Table 3.
Parameter estimates from the final PK−PD model and bootstrap analysis
| Parameters | Final estimates | Shrinkage (%) | Bootstrap estimates* | |
|---|---|---|---|---|
| Median | 95% CI | |||
| E0 (nmol h−1 mg−1 protein) | 3.45 | 3.48 | 2.61, 4.56 | |
| EC50 (mg l−1) | 1.73 | 1.73 | 1.16, 3.01 | |
| Emax (nmol h−1 mg−1 protein) | 0 fix | – | – | |
| Inter-individual variability (%CV)† | ||||
| ω (E0) | 39.6 | 13% | 37.8 | 9.6, 56.2 |
| ω (EC50) | 72.5 | 26% | 76.3 | 18.1, 152.5 |
| ω (Emax) | 0 fix | – | – | |
| Proportional residual error (%CV)c | ||||
| σprop | 42.2 | 8% | 41.7 | 34.6, 48.3 |
*
Obtained from 220 out of 300 non-parametric bootstrap runs.
†
Reported as %CV, calculated by the equation 100*SQRT(exp(ωn) − 1) where ωn is the nonmem output for the inter-subject variability of the n th parameter.
c
Calculated by the equation 100 × SQRT(σ), where σ is the nonmem output for the variance of the proportional residual error. E0 is the baseline IMPDH activity; Emax is the maximal fractional inhibitory effect; EC50 is the MPA concentration at half Emax; %CV: coefficient of variation; CI: confidence interval.