Pharmacokinetic parameters of PNU-288034 in mouse, rat, dog, and monkey
Plasma and urine samples were collected, and concentration-time curves were determined. Pharmacokinetic parameters were derived as described under Materials and Methods. Absolute oral bioavailability (F) was calculated by using dose and AUC values.
| Route | Dose | Cmax | Tmax | t1/2 | MRT | Vss | CL | Unchanged in Urine | F | |
|---|---|---|---|---|---|---|---|---|---|---|
| mg/kg | μg/ml | h | h | h | l/kg | ml/min/kg | % | % | ||
| CF-1 mouse | IV | 4 | 5.31 ± 0.1 | 0.76 | 0.69 | 1.36 | 32.9 | ND | ||
| PO | 4 | 2.49 ± 0.1 | 0.17 | 0.92 | 1.1 | — | — | ND | 96 | |
| Sprague-Dawley rat | IV | 9.6 | 19.9 ± 1.5 | 8.05 ± 0.00 | 1.15 ± 0.09 | 1.30 ± 0.26 | 18.9 ± 2.4 | 81.9 ± 0.2 | ||
| PO | 21.3 | 9.10 ± 2.0 | 0.50 | 5.90 ± 1.4 | 2.63 ± 0.26 | — | — | 73.2 ± 6.4 | 73.3 ± 9.3 | |
| Beagle dog | IV | 9.7 | 49.5 ± 2.0 | 6.51 ± 0.28 | 1.72 ± 0.00 | 0.57 ± 0.02 | 5.58 ± 0.23 | 95.0 ± 16 | ||
| PO | 10 | 7.60 ± 1.4 | 0.50 | 2.70 ± 1.8 | 2.29 ± 0.18 | — | — | 88.7 ± 5.7 | 72.9 ± 6.9 | |
| Monkey | IV | 10 | 35.7 ± 8.8 | 5.49 ± 2.05 | 2.18 ± 0.29 | 0.855 ± 0.089 | 6.55 ± 0.40 | 42.0 ± 16.7 |
IV, intravenous; PO, oral; ND, not determined.