TABLE 4
Pharmacokinetic parameters of 4-ME and 4-ME-G in wild-type, Bcrp1−/−, and Mrp2−/− FVB mice after i.v. injection of 2 mg/kg (10.41 μmol/kg) 4-ME
Data are presented as means ± S.D. (n = 5); unpaired Student’s t test was used to analyze the data.
| Parameters | 4-ME | 4-ME-G | ||||
|---|---|---|---|---|---|---|
| FVB | Bcrp1−/− | Mrp2−/− | FVB | Bcrp1−/− | Mrp2−/− | |
| AUC0–t (min • μmol/l) | 50.40 ± 10.48 | 75.22 ± 14.08 | 82.45 ± 21.16 | 53.66 ± 13.56 | 161.98 ± 32.97* | 174.35 ± 34.12 |
| AUC0–∞ (min • μmol/l) | 57.66 ± 11.13 | 84.70 ± 15.97 | 89.99 ± 25.31 | 55.08 ± 13.80 | 162.83 ± 33.01* | 175.29 ± 33.66* |
| T1/2 (min) | 410.00 ± 249.10 | 329.55 ± 153.40 | 93.86 ± 28.40 | 96.00 ± 51.36 | 58.16 ± 12.00 | 30.27 ± 7.64 |
| MRT (min) | 169.63 ± 39.07 | 160.18 ± 27.25 | 83.30 ± 20.05 | 45.81 ± 4.72 | 43.37 ± 5.16 | 33.58 ± 6.89 |
| Vd (l/kg) | 61.44 ± 21.08 | 44.9 ± 10.71 | 19.48 ± 8.07* | N/A | — | — |
| CL (l/min per kilogram) | 0.12 ± 0.04 | 0.09 ± 0.03 | 0.10 ± 0.02 | — | — | — |
| M/P AUC ratios | 0.96 | 1.92 | 1.95 | — | — | — |
 | 22.28 | 45.70 | 22.97 | |||
M/P AUC ratios, the AUC0–∞ ratio of 4-ME-G to 4-ME; T1/2, half-life.
* P < 0.05 indicates a statistically significant difference between wild-type FVB mice and Bcrp1−/− mice (or Mrp2−/− mice).