TABLE 1

Steady-state brain distribution of gefitinib in wild-type and Mdr1a/b(−/−) Bcrp1(−/−) FVB mice after a continuous intraperitoneal infusion of gefitinib

Steady-state brain concentrations were 16-fold lower than the plasma concentrations in the wild-type mice. Brain concentrations at steady-state in the Mdr1a/b(−/−) Bcrp1(−/−) mice were 7-fold greater than the plasma concentrations and up to 100-fold greater than the brain concentrations in wild-type mice (mean ± S.E.).

GroupTimenPlasma CssBrain CssBrain-to-Plasma Ratio
hμg/mlμg/g
Wild-type (control)2450.49 ± 0.080.03 ± 0.01*0.07 ± 0.02
4840.21 ± 0.050.01 ± 0.01*0.10 ± 0.05a
Mdr1a/b(−/−)Bcrp1(−/−)2440.24 ± 0.071.7 ± 0.5*7.3 ± 0.5
4840.19 ± 0.101.2 ± 0.6*7.1 ± 0.9a
  • * , p < 0.05 compared to plasma;

  • , p < 0.05 compared to wild type.

  • a ns, not significant compared to 24-h time point.