Parameter | Wild Type | Mrp2 KO | Bcrp KO | Mdr1a KO |
---|---|---|---|---|
Carboxydichlorofluorescein (3 mg/kg i.v.; bile duct-intact rats) | ||||
AUCinf, μg · h/ml | 31.6 ± 3.9 | 41.8 ± 4.5* | 22.8 ± 4.2* | 22.6 ± 4.0* |
CL, ml · min−1 · kg−1 | 1.6 ± 0.2 | 1.2 ± 0.1* | 2.3 ± 0.5* | 2.3 ± 0.3* |
VD, SS, ml/kg | 170 ± 8 | 190 ± 20 | 184 ± 22 | 192 ± 18 |
t1/2, h | 1.4 ± 0.2 | 1.9 ± 0.2* | 1.1 ± 0.1 | 1.2 ± 0.1 |
Carboxydichlorofluorescein (3 mg/kg i.v.; bile duct-cannulated rats) | ||||
Xurine0–4 h, % dosea | 30 ± 14 | 61 ± 24 | 52 ± 15 | N/A |
Xbile0–4 h, % dose | 56 ± 21 | 0 ± 0* | 45 ± 18 | N/A |
Total0–4 h, % dose | 86 ± 23 | 61 ± 24 | 97 ± 19 | N/A |
Xurine0–4 h, % dosea | 34 ± 11 | N/A | N/A | 32 ± 20 |
Xbile0–4 h, % dose | 20 ± 11 | N/A | N/A | 18 ± 18 |
Total0–4 h, % dose | 54 ± 5 | N/A | N/A | 50 ± 23 |
KO, knockout; AUCinf, area under the curve extrapolated to infinity; CL, clearance; VD, SS, volume of distribution; t1/2, half-life; X, amount excreted; N/A, not applicable. .
↵* p < 0.05.
↵a Amount excreted in urine also includes urine dried on the side of the metabolic cage, which was recovered in the cage wash at the end of the study.