Parameters | Wild Type n = 6 | Abcg2−/− n = 5 | Abcc4−/− n = 5 | Abcg2−/−;Abcc4−/− n = 6 |
---|---|---|---|---|
Plasma | ||||
CL (ml/min) | 1.96 ± 0.38 | 1.58 ± 0.52 | 2.00 ± 0.40 | 1.00 ± 0.20* |
Vd (l) | 0.54 ± 0.40 | 0.28 ± 0.14 | 0.73 ± 0.29 | 0.18 ± 0.09* |
Half-life(MTX,plasma) (min) | 195 ± 171 | 124 ± 28 | 247 ± 81 | 116 ± 28* |
AUCMTX(0–inf) (min*μg/ml) | 633 ± 121 | 836.9 ± 208 | 631 ± 185 | 1259 ± 289** |
AUC7-OH-MTX(0–inf) (min*μg/ml) | 26.1 ± 8.7 | 59.9 ± 23.7 | 22.2 ± 6.2 | 81.5 ± 23.9** |
Half-life7OH MTX (min) | 224 ± 131 | 237 ± 74.7 | 242 ± 96 | 200 ± 74 |
AUC7OH/AUCMTX (%) | 4.16 ± 1.35 | 7.80 ± 1.59 | 3.55 ± 0.6 | 6.52 ± 1.10 |
Brain | ||||
AUCbrain (min*μg/ml) | 66.85 ± 26 | 134 ± 54.80 | 118.12 ± 60.50 | 286.13 ± 130** |
Half-lifebrain (min) | 151 ± 69 | 104 ± 44 | 62.3 ± 22.7 | 88 ± 15 |
Cmax (μg/ml) | 1.2 ± 0.5 | 1.8 ± 0.9 | 1.5 ± 0.6 | 3.7 ± 2.2 |
Kp,brain | 0.11 ± 0.05 | 0.17 ± 0.08 | 0.19 ± 0.09 | 0.23 ± 0.09* |
↵* P < 0.05; **P < 0.01.