TABLE 3

Vu,brain values for the model compounds determined by microdialysis, by the slice uptake and homogenate binding methods, and by predictions from log D7.4

The values are given in ml · g brain−1 and are presented as means ± S.D. The microdialysis values are taken from the literature according to the references given. Unless otherwise indicated, continuous intravenous infusions of drug were administered to rats, and sampling of whole brain tissue and striatal microdialysate was undertaken at steady state.

In Vivo Microdialysis
In Vitro Brain Slice Uptake (n = 5-7)
In Vitro Brain Homogenate Binding (n = 3)
Predicted from Log D7.4
Alovudine (A)a,b,c (Linden et al., 2003) 0.52d 1.07 ± 0.091 1.05 ± 0.30 0.66
R-Apomorphine (R-A)c,e (Sam et al., 1997) 15d 18.1 ± 1.9 15.5 ± 0.38 16.8
S-Apomorphine (S-A)c,e (Sam et al., 1997) 26d 14.0 ± 1.4 14.4 ± 0.76 15.5
R-Cetirizine (R-C)b,c,f,g (Gupta et al., 2006) 2.39h 6.62 ± 0.56 11.8 ± 0.80 5.99
S-Cetirizine (S-C)b,c,f,g (Gupta et al., 2006) 2.86h 6.56 ± 0.61 11.8 ± 0.80 4.90
Codeine (C)i (Xie and Hammarlund-Udenaes, 1998) 3.6 ± 1.2h 2.77 ± 0.22 1.46 ± 0.18 1.41
CP-122721 (CP)c 207 ± 14j 210 ± 17 152 ± 19 21.3
Diazepam (D)k,l (Dubey et al., 1989) 22d 17.7 ± 0.80 24.6 ± 1.2 28.1
Gabapentin (G)c (Wang and Welty, 1996) 5.5 ± 2.0h 3.97 ± 0.77m 1.04 ± 0.14 0.27
Morphine (M)c (Tunblad et al., 2003) 1.7h 2.69 ± 0.43 2.00 ± 0.20 0.67
Morphine-3-glucuronide (M3G)c (Xie et al., 2000) 0.25 ± 0.02h 0.528 ± 0.059 1.27 ± 0.18 0.36
Morphine-6-glucuronide (M6G)c (Bouw et al., 2001) 0.20 ± 0.02h 0.731 ± 0.078 1.24 ± 0.10 0.57
Norfloxacin (N)n,o (Ooie et al., 1997) 0.98 ± 0.59h 2.01 ± 0.10 1.72 ± 0.37 0.31
Oxycodone (O)i (Bostrom et al., 2006) 2.20 ± 0.53h 3.60 ± 0.35 1.95 ± 0.33 4.60
Thiopental (T)p
(Mather et al., 2000)
10d
5.07 ± 0.29
6.51 ± 0.89
34.8

  • ↵ a Drug administration by subcutaneous bolus dose.

  • ↵ b Estimation of Vu,brain during non-steady-state conditions.

  • ↵ c Probe calibration by in vivo retrodialysis by drug.

  • ↵ d Vu,brain calculated from data in original literature report.

  • ↵ e Drug administration by continuous subcutaneous infusion.

  • ↵ f Experiments performed in guinea pigs.

  • ↵ g Drug administration by short intravenous infusion.

  • ↵ h Vu,brain reported in original literature.

  • ↵ i Probe calibration by in vivo retrodialysis by calibrator.

  • ↵ j Vu,brain experimentally obtained from original data in this study.

  • ↵ k Probe calibration in vitro.

  • ↵ l Probe placement in cortex.

  • ↵ m Vu,brain calculated from slices incubated for 1 h.

  • ↵ n Probe calibration in vivo by reference compound.

  • ↵ o Probe placement in hippocampus.

  • ↵ p Probe calibration by in vivo retrodialysis by drug and correction.