Table 2. Population pharmacokinetics parameters of Pt estimated from the final model and bootstrap validation (500 resamplings).
| Bootstrap analysis |
||||
|---|---|---|---|---|
| Parameter | Original data set estimate (%RSE) | Mean | 95% CI | Shrinkage (%) |
| Structural model | ||||
| IPV (l) | 3.10 (3.1) | 3.11 | 2.94 to 3.26 | |
| IPCL (l h–1)= θ1+ θ2 x EPI | ||||
| θ1 | 4.66 (4.3) | 4.66 | 4.34 to 5.02 | |
| θ2 | –0.531 (6.9) | –0.533 | –0.471 to –0.586 | |
| CL (l h–1) | 9.63 (5.2) | 9.61 | 8.77 to 10.49 | |
| V (l) = θ3+ θ4 x EPI | ||||
| θ3 | 21.4 (5.9) | 21.40 | 19.40 to 24.49 | |
| θ4 | 0.805 (26.3) | 0.778 | 0.472 to 1.188 | |
| k23 (h−1) | 0.632 (3.7) | 0.635 | 0.595 to 0.678 | |
| k32 (h−1) | 0.0425 (4.4) | 0.0424 | 0.0395 to 0.0450 | |
| Vmax (mg l–1) | 0.0123 (9.2) | 0.0124 | 0.0106 to 0.0142 | |
| KM (mg l–1) | 2.00 (10.1) | 1.98 | 1.66 to 2.37 | |
| kB (l h–1) | 0.382 (7.2) | 0.381 | 0.330 to 0.437 | |
| Interindividual variability | ||||
| IIVIPV (%CV) | 19.7 (25.9) | 19.1 | 14.9 to 23.2 | 9.7 |
| IIVIPCL (%CV) | 22.3 (19.0) | 21.9 | 17.9 to 25.3 | 11.0 |
| IIVCL(%CV) | 39.4 (28.2) | 38.0 | 30.1 to 47.3 | 9.1 |
| IIVV (%CV) | 26.4 (42.5) | 26.5 | 17.0 to 38.1 | 6.8 |
| IIVBmax (%CV) | 51.3 (12.2) | 50.8 | 44.6 to 56.9 | 0.7 |
| ρ V/Vmax | –0.124 (29.3) | –0.123 | –0.062 to –0.197 | |
| Residual errors | ||||
| ε1 (%CV) | 17.8 (9.6) | 17.7 | 16.4 to 19.2 | 7.3 |
| ε2 (mg l–1) | 0.098 (7.0) | 0.098 | 0.083 to 0.114 | |
Abbreviations: θ=value of the parameter associated with the equation of the covariate; ε1=exponential part of the residual error; ε2=additive part of the residual error; CI=confidence interval; %CV=percentage of coefficient of variation; CL=clearance associated with the serum (central) compartment; IPCL=IP clearance; IIV=interindividual variability; Pt=platinum; %RSE=relative standard error; V and IPV=volume of distribution associated with the serum central and IP compartments; Vmax and KM=the Michaelis–Menten constants used to model covalent binding to protein; kB=the elimination constant rate of Pt-bound Pt to protein; k23, k32=rate constants between central and peripheral compartments.