TABLE 3.
Steady-state plasma and brain concentration, brain-to-plasma ratio, and distribution advantage of ponatinib after continuous intraperitoneal infusion (40 µg/h) for 48 h in FVB wild-type, Bcrp1(−/−), Mdr1a/b(−/−), and Mdr1a/b(−/−)Bcrp1(−/−) mice (N = 4 in each genotype)
Data are presented as the mean ± S.D, unless otherwise indicated.
| Mice | Steady-State Total Concentration (μg/ml) |
Kp | Kp,uua | DAb | |
|---|---|---|---|---|---|
| Plasma | Brain | ||||
| FVB wild-type | 0.72 ± 0.66 | 0.53 ± 0.37 | 1.0 ± 0.51 | 0.11 ± 0.056 | |
| Bcrp1(−/−) | 0.42 ± 0.21 | 0.71 ± 0.30 | 1.8 ± 0.26 | 0.20 ± 0.029 | 1.7 |
| Mdr1a/b(−/−) | 0.39 ± 0.14 | 1.3 ± 0.70 | 3.8 ± 2.5 | 0.42 ± 0.28 | 3.7 |
| Mdr1a/b(−/−)Bcrp1(−/−) | 0.40 ± 0.34 | 6.1 ± 5.0* | 15.6 ± 2.6* | 1.7 ± 0.29* | 15.0 |
a
Calculated by Kp × [fu,brain/fu,plasma].
b
DA due to lack of transporters, or Kp,knockout/Kp,wild-type or Kp,uu,knockout/Kp,uu,wild-type.
*
Statistical difference (P < 0.05) compared with the FVB wild-type mice.