TABLE 6

Pharmacokinetic parameters obtained from the compartmental BBB model describing the brain and plasma concentration-time after administration of a single intravenous bolus (3 mg/kg, i.v.; N = 3 to 4 at each time point) or oral dose (30 mg/kg, PO; N = 4 at each time point) in FVB wild-type, Bcrp1(−/−), Mdr1a/b(−/−), and/or Mdr1a/b(−/−)Bcrp1(−/−) mice

Fixed values are left as blank (—). The parameters are presented as the mean estimate.

Route of AdministrationGenotypeParameters
kin (h−1)kout (h−1)MTTbrain (h)aCLin (ml/h per kilogram)CLout (ml/h per kilogram)CLu,in (ml/h per kilogram)CLu,out (ml/h per kilogram)
MeanCV (%)MeanCV (%)MeanMeanCV (%)MeanCV (%)MeanCV (%)MeanCV (%)
IntravenousWT4.0 × 10−57.710.20.130.0590.06636.625.8225.822.5
TKO4.0 × 10−511.20.6414.01.60.05913.80.005537.925.811.218.724.4
By mouthWT5.5 × 10−512.42.70.0810.0810.1135.335.2361.620.2
Bcrp-KO5.5 × 10−58.218.20.120.0810.07039.635.2239.427.0
Pgp-KO5.5 × 10−52.926.00.340.0810.02543.835.285.132.8
TKO5.5 × 10−516.20.6515.71.50.08118.10.005638.535.216.219.025.5
  • Bcrp-KO, Bcrp1(−/−); KO, knockout; Pgp-KO, Mdr1a/b(−/−); TKO, Mdr1a/b(−/−)Bcrp1(−/−); WT, wild-type.

  • a Calculated by 1/kout.