TABLE 3

Influence of rat albumin on brain tissue binding

Binding affinities to brain lipids [KD(lipid)] and RSA [KD(RSA)] were determined by TRANSIL experiments and the free fractions based on binding to lipids only [fu(lipid)]. The values for binding to lipids and brain tissue albumin [fu(lipid + RSA)] were calculated according to eq. 6. The free fraction determined by equilibrium dialysis [fu(ED)] was assessed using perfused rat brains. The difference in the unbound fraction between binding to lipids only and binding to lipids and brain tissue albumin is denoted by ΔRSA.

Compoundfu(ED)KD(lipid)KD(RSA)fu(lipid)fu(lipid + RSA)ΔRSA
%MM%%%
Amitriptyline0.871.01 10−061.34 10−040.830.830.00
Carbamazepine17.282.42 10−051.03 10−0416.7816.760.02
Chlorpromazine0.161.84 10−071.17 10−050.150.150.00
Clozapine0.677.75 10−077.88 10−050.640.640.00
Diazepam2.743.24 10−061.51 10−052.632.630.00
Fluoxetine0.283.23 10−073.61 10−050.270.270.00
Haloperidol1.341.56 10−069.69 10−051.291.290.00
Ibuprofen31.175.27 10−051.47 10−0630.5526.104.44
Metoclopramid43.168.89 10−051.37 10−0342.5742.560.01
Risperidon12.461.64 10−054.38 10−0512.0612.030.03
Thioridazin0.323.69 10−076.69 10−060.310.310.00
Tolbutamid84.436.46 10−047.97 10−0684.3477.616.73
Trazodon4.545.47 10−067.95 10−064.374.350.02
Trifluorperazine0.343.92 10−071.40 10−050.330.330.00
Venlafaxin24.783.82 10−055.11 10−0424.1924.180.01
Warfarin41.058.14 10−059.31 10−0640.4539.061.39