TABLE 4

Estimated in vivo Kp,uu,brain from observed Kp brain and unbound fractions, and reconstructed Kp,uu,brain from in vitro data

The in vivo Kp,uu,brain was estimated from the plasma and brain unbound fractions (see Table 3) and the observed Kp brain in wild-type mice (see Table 1) according to eq. 12. The reconstructed Kp,uu,brain was obtained as the reciprocal of the reconstructed Kp brain ratio according to eq. 13 with the assumption that drugs are transported only by mdr1a. Each value represents the mean ± S.E.M. The S.E.M. was calculated according to the law of propagation of error.

SubstrateEstimated In Vivo Kp,uu,brainReconstructed Kp,uu,brain
Quinidine0.0587 ± 0.00470.0325 ± 0.0032
Loperamide0.0164 ± 0.00130.0429 ± 0.0040
Digoxin0.00469 ± 0.000220.0603 ± 0.0070
Risperidone0.212 ± 0.0110.101 ± 0.008
Indinavir0.119 ± 0.0180.112 ± 0.012
Dexamethasone0.0933 ± 0.00360.0897 ± 0.0069
Vinblastine<0.0248a0.0864 ± 0.0149
Paclitaxel0.116 ± 0.0150.0870 ± 0.0095
Verapamil0.100 ± 0.0110.0805 ± 0.0069
Loratadine0.740 ± 0.0260.589 ± 0.050
Diazepam1.16 ± 0.101.15 ± 0.05
  • a The estimated in vivo Kp,uu,brain of vinblastine was less than 0.0248 because it was estimated by using the reported plasma unbound fraction of more than 0.09 (Kalvass et al., 2007).