TABLE 2

Unbound fractions and the corresponding in vivo exposure ratios for 33 CNS drugs in mice

Free fraction data are reported as mean ± S.D. (n = 5 or 6, unless otherwise indicated by an = 18 or cn = 12) with the number of significant figures being determined by the observed variability. Standard deviation for the ratio of fuplasma to fubrain was determined by Taylor approximation. In vivo exposure ratios were obtained from the accompanying work (Doran et al., 2005). bIn vivo ratio observed at 1 h due to insufficient analytical sensitivity necessary to determine CSF area under the curve.

fuplasma/fubrain
[Brain]/[Plasma]
fubrain
[CSF]/[Brain]
fuplasma
[CSF]/[Plasma]
Buspirone 1.24 ± 0.06 1.6 0.22 ± 0.02 0.031 0.273 ± 0.018 0.051
Caffeine 2.2 ± 0.2 1.0 0.52 ± 0.12 0.082 1.13 ± 0.03 0.079
Carbamazepine 2.79 ± 0.09 0.76 0.116 ± 0.0081 0.46 0.324 ± 0.014 0.35
Carisoprodol 1.93 ± 0.06 0.66 0.202 ± 0.015 0.43 0.389 ± 0.003 0.28
Chlorpromazine 47 ± 8 23 0.00076 ± 0.00018 0.0011 0.0354 ± 0.0119 0.025
Citalopram 7.6 ± 0.3 5.1 0.0306 ± 0.0018 0.10 0.231 ± 0.013 0.53
Clozapine 4.0 ± 0.2 4.1 0.0094 ± 0.0013 0.018 0.038 ± 0.002 0.075
Cyclobenzaprine 7.4 ± 0.4 12 0.0073 ± 0.0004 0.0049 0.054 ± 0.006 0.057
Diazepam 1.96 ± 0.07 2.0 0.050 ± 0.003 0.034 0.098 ± 0.007 0.066
Fluoxetine 13.5 ± 1.2 12 0.0023 ± 0.0005 0.0027 0.031 ± 0.002 0.031
Fluvoxamine 4.6 ± 0.2 6.1 0.0084 ± 0.0008 0.01 0.0387 ± 0.0019 0.058
Haloperidol 12.3 ± 1.3 13 0.0071 ± 0.0017 0.011 0.087 ± 0.009 0.14
Hydrocodone 1.07 ± 0.06 2.1 0.55 ± 0.06 0.27 0.59 ± 0.04 0.56
Hydroxyzine 5.1 ± 0.3 7.7 0.0102 ± 0.0012 0.0095 0.052 ± 0.005 0.073
Lamotrigine 1.73 ± 0.16 1.1 0.22 ± 0.04 0.14 0.38 ± 0.05 0.15
Meprobamate 1.00 ± 0.05 0.42 0.76 ± 0.04 0.93 0.76 ± 0.08 0.39
Methylphenidate 3.50 ± 0.14 12 0.220 ± 0.006 0.090 0.77 ± 0.07 1.1
Metocloperamide 2.29 ± 0.16 1.2 0.31 ± 0.05 0.36 0.71 ± 0.03 0.44
Midazolam 1.69 ± 0.08 0.23 0.0272 ± 0.0018 0.25 0.046 ± 0.004 0.056
Morphine 0.64 ± 0.04 0.46 0.50 ± 0.07 1.4 0.32 ± 0.03 0.64
Nortriptylinea 6.7 ± 0.9 11 0.0046 ± 0.0006 0.0021 0.031 ± 0.009 0.024
Paroxetine 3.8 ± 0.3 3.3 0.0039 ± 0.0002 0.0044 0.015 ± 0.003 0.015
Phenytoin 2.26 ± 0.05 0.63 0.081 ± 0.004 0.28 0.183 ± 0.006 0.18
Propoxyphene 3.4 ± 0.3 2.9 0.033 ± 0.006 0.070 0.111 ± 0.005 0.20
Risperidone 3.04 ± 0.15 0.78 0.067 ± 0.007 0.025 0.204 ± 0.011 0.019
9-OH-Risperidone 3.84 ± 0.17 0.06 0.086 ± 0.004 0.74 0.33 ± 0.03 0.045
Selegiline 2.86 ± 0.10 3.7 0.056 ± 0.004 0.12 0.160 ± 0.008 0.44
Sertraline 16.7 ± 1.8 24 0.00066 ± 0.00012 0.00020b 0.011 ± 0.002 0.0058b
Sulpiride 1.21 ± 0.09 0.078 0.63 ± 0.10 0.48 0.76 ± 0.05 0.038
Thiopentalc 2.078 ± 0.006 0.36 0.14630 ± 0.00010 0.13 0.304 ± 0.002 0.046
Trazodone 1.09 ± 0.10 0.61 0.047 ± 0.009 0.061 0.051 ± 0.007 0.037
Venlafaxinec 4.3 ± 0.4 4.2 0.21 ± 0.03 0.099 0.90 ± 0.13 0.41
Zolpidema
1.20 ± 0.08
0.29
0.20 ± 0.03
1.3
0.24 ± 0.02
0.37