Table 2.
Pharmacokinetic parameters of PTX after IV injection (2 mg/kg), and after oral administration of PTX (25 mg/kg) alone, or with other compounds (VER, AC-603 or AC-786) in rats (n=4–5)
| PK parameters | PTX IV | PTX PO alone | PTX with VER | PTX with AC-603 | PTX with AC-786 | |||
|---|---|---|---|---|---|---|---|---|
|
|
|
|
||||||
| 0.5 mg/kg | 5 mg/kg | 0.5 mg/kg | 5 mg/kg | 0.5 mg/kg | 5 mg/kg | |||
| C0(ng/mL) | 3328.1 ± 1160.1 | - | - | - | - | - | - | - |
| Cmax (ng/mL) | - | 60.6 ± 10.3 | 84.7 ± 14.4 | 125.3 ± 63.0 | 167.1 ± 58.6* | 133.9 ± 55.2 | 144.1 ± 39.2 | 180.1 ± 37.2** |
| Tmax (h) | - | 4.2 ± 1.1 | 5.0 ± 2.6 | 3.3 ± 0.5 | 4.3 ± 1.3 | 4.3 ± 1.3 | 3.0 ± 0.0 | 3.0 ± 0.0 |
| AUClast(ng·hr/mL) | 1655.7 ± 498.8 | 408.9 ± 47.2 | 604.9 ± 111.7 | 715.3 ± 259.9* | 824.2 ± 198.2* | 903.8 ± 161.7** | 716.9 ± 194.0* | 738.7 ± 73.8* |
| AUCinf(ng·hr/mL) | 1794.3 ± 522.0 | 564.4 ± 115.8 | 785.9 ± 125.7 | 875.6 ± 304.5 | 933.5 ± 215.7* | 1021.8 ± 158.1* | 910.1 ± 158.0 | 831.7 ± 72.2 |
| t1/2(h) | 4.55 ± 1.02 | 4.26 ± 1.62 | 5.45 ± 2.86 | 3.28 ± 0.88 | 2.41 ± 0.70 | 3.09 ± 0.83 | 4.16 ± 1.71 | 2.84 ± 0.28 |
| Ke(1/h) | 0.161 ± 0.047 | 0.182 ± 0.066 | 0.153 ± 0.071 | 0.227 ± 0.078 | 0.312 ± 0.112 | 0.234 ± 0.050 | 0.191 ± 0.085 | 0.246 ± 0.025 |
| Vd(L) | 2.06 ± 0.36 | - | - | - | - | - | - | - |
| Vd/F (L) | - | 73.6 ± 14.9 | 64.6 ± 27.2 | 39.4 ± 19.0* | 24.8 ± 10.0** | 28.7 ± 7.1** | 45.3 ± 21.1* | 33.0 ± 6.3* |
| Clt(L/h) | 0.328 ± 0.097 | - | - | - | - | - | - | - |
| Clt/F (L/h) | - | 12.7 ± 2.8 | 8.5 ± 1.4** | 8.3 ± 3.3** | 7.1 ± 1.4** | 6.5 ± 1.2** | 7.4 ± 1.1** | 8.0 ± 0.8** |
| Absolute BA (%) | - | 2.0 | 2.9 | 3.5 | 4.0 | 4.4 | 3.5 | 3.6 |
| Relative BA (%) | - | 100.0 | 147.5 | 174.7 | 201.0 | 220.7 | 174.7 | 180.3 |
*
p<0.05,
**
p<0.01 compared with PTX PO (25 mg/kg) alone, Data are presented as mean ± SD (n=4–5).