Table I.
Physiological Parameters Used for Allometric Scaling of TOF PK and Corresponding Parameter Estimates (CV%)
| Parameters (units) | Definition | Rat (0.25 kg) | Mouse (0.02 kg) | Human (70 kg) |
|---|---|---|---|---|
| Fpo | Oral bioavailability | 60.9%a 67.8%b |
57.2%c | 74% d |
| Ka,poe (/h) | Oral absorption rate constant | 3.27 | 3.96 | 1.36 |
| Fd,RPT | Fraction of cardiac blood flow accessing rapidly-perfused tissues (RPT) | 0.82 | 0.80 | 0.77 |
| fd,SPT | Fraction of cardiac blood flow accessing slowly-perfused tissues (SPT) | 0.18 | 0.20 | 0.23 |
| Vb (mL) | Blood volume | 13.5 | 1.7 | 5200 |
| Vrpt (mL) | Volume of lumped rapidly-perfused tissues | 64.5 | 4.0 | 17,000 |
| Vspt (mL) | Volume of lumped slowly-perfused tissues | 172 | 14.3 | 47,800 |
| Qco (mL/h) | Cardiac blood flow | 4440 | 480 | 336,000 |
| Kp,RPT | Tissue: blood partition coefficient in RPT | 1.84 (27.8) | ||
| Kp,SPT | Tissue: blood partition coefficient in SPT | 2.21 (6.8) | ||
| a | Allometric coefficient | 1462 (4.5) | ||
| b | Allometric exponent | 0.75 (1.5) | ||
| CL (mL/h/kg) | Predicted clearance | 2062.4 | 3860.5 | 509.4 |
Physiological parameter values were obtained from Davies and Morris (20), Kawai et al. (21), and Shah and Betts (22)
a
Fpo value calculated based on Sharma et al. (15)
b
Fpo value calculated based on Kumar et al. (14)
c
Fpo value from Dixit et al. (16)
e
ka,po values estimated in preliminary PK fitting within species