TABLE 6

Brain/plasma ratios of [14C]lapatinib after a single i.v. dose of 1 or 10 mg/kg to male wild-type and Pgp-deficient mice

Data are the means (±S.D) from three male animals or mean (range) from two male animals due to a missed dose of one animal.

Dose and Time Wild-Type FVB Mice mdr1a/1b(-/-) Mice Knockout/Wild-Type Brain/Plasma Ratio
Plasma Concentrations Brain Concentrations Average Brain/Plasma Ratio Plasma Concentrations Brain Concentrations Average Brain/Plasma Ratio
ng/ml ng/g ng/ml ng/g
1 mg/kg
    0.5 h 312 (35) 13.9 (3.7) 0.04 (0.01) 429 (16) 102 (11) 0.24 (0.03) 5.53
    2 h 68.9 (13.4) 6.26 (2.62) 0.09 (0.02) 76.3 (14.6) 41.9 (7.9) 0.56 (0.15) 6.36
10 mg/kg
    0.5 h 4559 (745) 1012 (116) 0.22 (0.06) 4916 (314) 2640 (239) 0.54 (0.06) 2.63
    2 h 1869 (1502-2235) 463 (332-594) 0.25 (0.22-0.27) 1871 (414) 1762 (595) 0.94 (0.20) 2.86