Table 3.
Population pharmacokinetic parameters for cilostazol in 104 subjects and the results of bootstrap validation (final model)
| Final model | Bootstrap replicates | |||
|---|---|---|---|---|
| Parameter | Estimate | CI (95%)* | Median | CI (95%)† |
| TV (CL/F) (l h−1) | 12.8 | 8.2, 17.4 | 12.7 | 8.9, 18.5 |
| TV (Vc/F) (l) | 20.5 | 16.4, 24.6 | 20.6 | 16.6, 25.3 |
| TV (Q/F) (l h−1) | 5.64 | 3.81, 7.47 | 5.88 | 4.34, 7.85 |
| TV (Vp/F) (l) | 73.1 | 32.14, 114 | 75.3 | 42.8, 126 |
| TV (Ka) (h−1) | 0.244 | 0.215, 0.273 | 0.248 | 0.214, 0.285 |
| TV (TLag) (h) | 0.565 | 0.507, 0.623 | 0.566 | 0.480, 0.628 |
| CL/F, θIMs | −0.147 | −0.247, −0.047 | −0.143 | −0.241, −0.016 |
| CL/F, θPMs | −0.272 | −0.460, −0.084 | −0.275 | −0.552, −0.020 |
| CL/F, θ*1/*3 | −0.223 | −0.507, 0.061 | −0.203 | −0.460, −0.070 |
| CL/F, θ*3/*3 | −0.407 | −0.627, −0.187 | −0.388 | −0.592, −0.153 |
| ω2CL/F | 0.075 | 0.039, 0.111 | 0.067 | 0.018, 0.102 |
| ω2Vc/F | 0.481 | 0.327, 0.635 | 0.488 | 0.337, 0.705 |
| ω2Q/F | 1.16 | 0.49, 1.83 | 1.15 | 0.66, 1.87 |
| ω2Vp/F | 0.688 | 0.284, 1.09 | 0.738 | 0.431, 1.43 |
| ωVp/F, CL/F | 0.0685 | 0.0058, 0.131 | 0.367 | 0.019, 0.776 |
| ωQ/F, Vc/F | −0.355 | −0.528, −0.182 | −0.479 | −0.659, −0.267 |
| ωVp/F, Q/F | 0.460 | −0.089, 1.01 | 0.549 | −0.038, 0.851 |
| σ2pro | 0.0131 | 0.0036, 0.0226 | 0.0129 | 0.0040, 0.0337 |
| σ2add | 0.00261 | 0.00121, 0.00401 | 0.00254 | 0.00081, 0.00440 |
*
Estimate ± 1.96 × (standard error of the estimate).
†
The 2.5th and 97.5th percentile of the bootstrap parameter estimates. A total of 1000 replicates of bootstrap analysis. θCOVARIATE, influential factor for covariate. *1/*3, CYP3A5*1/*3; *3/*3, CYP3A5*3/*3. ω, interindividual variability; σ, residual variability; CI, confidence interval; IMs, intermediate metabolizers; PMs, poor metabolizers.