Paclitaxel pharmacokinetic and excretory parameters
Data are means ± S.D. n = 5 to 9 (n = 6 to 12; bile duct-cannulated rats).
| Parameter | Wild Type | Mdr1a KO | Bcrp KO | Mrp2 KO |
|---|---|---|---|---|
| Paclitaxel (1 mg/kg i.v.) | ||||
| AUCinf, ng · h/ml | 172 ± 67 | 303 ± 193 | 171 ± 40 | 375 ± 211 |
| CL, l · h−1 · kg−1 | 6.7 ± 2.6 | 4.0 ± 1.4* | 6.1 ± 1.5 | 9.1 ± 16 |
| VD, SS, l/kg | 30.3 ± 8.6 | 38.1 ± 12.7 | 29.1 ± 9.7 | 28.6 ± 18.0 |
| t1/2, h | 7.2 ± 3.1 | 12.2 ± 5.4 | 6.4 ± 2.2 | 8.1 ± 3.4 |
| Paclitaxel (1 mg/kg i.v.; bile duct-cannulated rats) | ||||
| Xurine0–24 h, % dose | 3.1 ± 1.6 | 0.14 ± 0.06* | 2.0 ± 0.8 | 4.5 ± 1.1 |
| Xbile0–24 h, % dose | 0.5 ± 0.5 | 0.00 ± 0.00* | 0.1 ± 0.1 | 0.2 ± 0.1 |
| Xfeces0–24 h, % dose | 2.3 ± 1.3 | 0.21 ± 0.17* | 1.0 ± 0.8 | 2.8 ± 0.7 |
| Paclitaxel (5 mg/kg p.o.) | ||||
| AUCinf, ng · h/ml | 88 ± 28 | 746 ± 649* | 113 ± 52 | 622 ± 394 |
| Cmax, ng/ml | 30 ± 6 | 145 ± 77* | 40 ± 14 | 151 ± 18* |
| Tmax, h | 0.8 ± 0.3 | 1.2 ± 1.1 | 0.9 ± 0.2 | 0.9 ± 1.6 |
| t1/2, h | 4.4 ± 3.6 | 10.0 ± 3.2* | 5.3 ± 3.2 | 9.4 ± 4.0 |
| F, % | 12 ± 4 | 47 ± 21* | 13 ± 4 | 27 ± 9 |
KO, knockout; AUCinf, area under the curve extrapolated to infinity; CL, clearance; VD, SS, volume of distribution; t1/2, half-life; X, amount excreted; Cmax, maximum concentration; Tmax, time to maximum concentration; F, bioavailability.
↵* p < 0.05.