The pharmacokinetic/metric parameters of E6201 in FVB wild-type and Mdr1a/b−/− Bcrp1−/− knockout mice following administration of single intraperitoneal dose of 40 mg/kg
Data are presented as mean or mean ± S.E.M. (n = 4).
| Plasma | Brain | |||
|---|---|---|---|---|
| Wild-type | Mdr1a/b−/− Bcrp1−/− | Wild-Type | Mdr1a/b−/− Bcrp1−/− | |
| Half-life (h) | 0.76 | 0.62 | 0.58 | 0.6 |
| Cmax (μg/ml) | 11.70 ± 2.25 | 18.40 ± 5.80 | 16.72 ± 1.36 | 30.75 ± 3.93 |
| Tmax (h) | 0.25 | 0.25 | 0.5 | 0.5 |
| AUC(0–t) (μg*h/ml) | 9.69 ± 0.73 | 11.73 ± 1.57 | 21.44 ± 1.13 | 44.93 ± 3.62 |
| AUC(0–∞) (μg*h/ml) | 9.73 | 11.75 | 21.46 | 44.99 |
| CL/F (ml/min per kilogram) | 68.5 | 56.75 | — | — |
| Vd/F (l/kg) | 4.5 | 3.1 | — | — |
| Kp (AUC(0–t) ratio) | - | - | 2.2 | 3.83 |
| Kp,uu (AUC(0–t) ratio) | - | — | 0.12 | 0.21 |
| DA | - | — | 1 | 1.75 |
| F | 0.95 | — | — | — |
AUC(0–t), area under the curve from zero to the time of last measured concentration; AUC(0–∞), area under the curve from zero to time infinity; CL/F, apparent clearance; Cmax, observed maximum concentration; DA (distribution advantage), the ratio of Kpknockout to Kpwild–type; F (absolute bioavailability), ratio of the dose corrected AUC(0–t),ip to dose corrected AUC(0–t),iv; Kp (AUC ratio), the ratio of AUC(0–t,brain) to AUC(0–t,plasma) using total drug concentrations; Kp,uu (AUC ratio), the ratio of AUC(0–t,brain) to AUC(0–t,plasma) using free drug concentrations; Tmax, time to reach the maximum concentration; Vd/F, apparent volume of distribution.