Table 5.
Final parameter estimates and bootstrap outcome for the CKD-519 overall (interspecies) PK model.
| Parameter | Description | Simple Allometry | Brain Weight-Corrected | ||
|---|---|---|---|---|---|
| Estimates | Bootstrap Median (90% Confidence Interval(CI)) | Estimates | Bootstrap Median (90% Confidence Interval(CI)) | ||
| CL * = θ1 × WT θ2 (/BrW) * | |||||
| θ1 | Coefficient for CL | 0.0308 | 0.0308 (0.0259–0.0379) |
0.488 | 0.490 (0.420–0.588) |
| θ2 | Exponent for CL | 0.525 | 0.526 (0.469–0.586) |
1.90 | 1.90 (1.83–1.95) |
| Vc = θ3 × WTθ4 | |||||
| θ3 | Coefficient for Vc | 0.0755 | 0.0763 (0.0628–0.0943) |
0.0735 | 0.0756 (0.0626–0.0954) |
| θ4 | Exponent of Vc | 1 (fix) | 1 (fix) | ||
| Q = θ5 × WTθ6 (/BrW) * | |||||
| θ5 | Coefficient for Q | 0.0549 | 0.0553 (0.0392–0.0760) |
0.846 | 0.837 (0.595–1.16) |
| θ6 | Exponent of Q | 0.670 | 0.663 (0.504–0.833) |
2.04 | 2.03 (1.85–2.21) |
| Vp = θ7 × WTθ8 | |||||
| θ7 | Coefficient for Vp | 0.829 | 0.832 (0.724–0.999) |
0.813 | 0.813 (0.719–0.960) |
| θ8 | Exponent of Vp | 1 (fix) | 1 (fix) | ||
| WB = (β/α) × (t/α) β − 1 | |||||
| α | Scale parameter of WB | 4.50 | 4.50 (4.21–4.80) |
4.51 | 4.49 (4.21–4.80) |
| β | Shape parameter of WB | 3.01 | 3.10 (2.89–3.32) |
3.11 | 3.10 (2.79–3.38) |
| F = Fmax × (1 − dose/(F50 + dose)) | |||||
| F max | Maximum bioavailability | 0.183 | 0.182 (0.151–0.219) |
0.192 | 0.192 (0.159–0.229) |
| F 50 | Amount of dose reaching 50% of the maximum bioavailability | 11.9 | 12.4 (9.55–16.2) |
10.6 | 10.8 (8.89–14.8) |
| ωCL (%) | Interindividual variability of CL | 42.8 | 42.2 (35.9–47.4) |
25.9 | 25.2 (19.8–31.4) |
| ωQ (%) | Interindividual variability of Q | 23.9 | 23.5 (19.5–26.6) |
60.8 | 0.579 (0.357–0.727) |
| ωα (%) | Interindividual variability of α | 27.1 | 26.5 (21.3–31.8) |
27.0 | 23.6 (8.40–27.6) |
| ωβ (%) | Interindividual variability of β | 65.7 | 62.4 (47.3–76.3) |
24.0 | 26.2 (3.00–34.1) |
BW, body weight; BrW, brain weight; MLP, maximum lifespan potential; CL, clearance (L/h); Vc, distribution volume in the central compartment (L); Q, distribution clearance (L/h); Vp, distribution volume in the peripheral compartment (L); WB, the time dependent absorption rate constant following Weibull distribution(1/h); F, absolute bioavailability; * reflected according to the allometry structure.