Class I | Class II | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Theobromine | Theophylline | Caffeine | Fluoxetine | Propranolol | CP-141938 | NFPS | ||||||
BPko/BPwta | 1.8b | 1.3b | 1.1c | 1.5c | 1.5b | 50d | 2.1b | |||||
In situ PSe (ml/h/kg) | 23 | 31 | 223 | 619 | 1043 | 6.4 | 31 | |||||
Plasma unbound fractionf | 0.92 | 0.29 | 0.96 | 0.060 | 0.15 | 0.56 | 0.041 | |||||
Brain unbound fractionb (Slice) | 0.62 | 0.31 | 0.71 | 0.0027 | 0.019 | 0.11 | 0.011 | |||||
Brain unbound fractionf (Homogenate) | 0.61 | 0.39 | 1.1 | 0.00094 | 0.036 | 0.22 | 0.0017 | |||||
AUC(Plasma, 0-∞) (ng · h/ml) | 4670 | 6990 | 3250 | 195 | 237 | 296 | 1480 | |||||
AUC(CSF, 0-∞) (ng · h/ml) | 5790 | 1420 | 3140 | 13.3 | 48.0 | 18.9 | 7.59 | |||||
AUC(Brain, 0-∞) (ng · hr/ml) | 2540 | 1910 | 2010 | 5140 | 3880 | 98.8 | 648 | |||||
Cu,brain/CCSFg (Slice) | 0.27 | 0.42 | 0.45 | 1.0 | 1.5 | 0.57 | 0.94 | |||||
Cu,brain/Cu, plasmag (Slice) | 0.37 | 0.29 | 0.46 | 1.2 | 2.1 | 0.066 | 0.12 | |||||
Cu,brain/CCSFh (Homogenate) | 0.27 | 0.52 | 0.70 | 0.36 | 2.9 | 1.1 | 0.15 | |||||
Cu,brain/Cu,plasmah (Homogenate) | 0.36 | 0.37 | 0.71 | 0.41 | 3.9 | 0.13 | 0.018 | |||||
CCSF/Cu,plasma | 1.3 | 0.70 | 1.0 | 1.1 | 1.4 | 0.11 | 0.13 |
↵ a BPko and BPwt represent the brain-to-plasma concentration ratio in mdr1a/1b gene knockout and FVB mice, respectively.
↵ b Becker and Liu (2006): unbound fraction in brain tissue determined using brain slices.
↵ e Liu et al. (2004): BBB permeability-surface area product, PS.
↵ f Liu et al. (2005): unbound fraction in plasma determined using equilibrium dialysis.
↵ g Cu,brain: the brain unbound fraction was determined from the brain slice method.
↵ h Cu,brain: the brain unbound fraction was determined from the brain homogenate method.