TABLE 5

Summary of species-specific plasma (fu,p) and brain homogenate (fu,b) unbound fractions, observed neuromatrix compound concentrations (CX,obs), and predicted Cb,u (Cb,u,pred) for large animal neuropharmacokinetic studies with risperidone

Compoundfu,pfu,bAnimaltaObservedPredictedRatio
CpCCSFCbCb,ubCb,ucCb,u,pred/Cb,u,obs
hng/mlng/mlng/gnMnM
Risperidone0.0830d0.0809eDogs 1/20.530.5/50.71.77/2.4458.7/45.011.6/8.871.42/2.360.12/0.27
Dogs 3/41.073.2/43.01.85/1.8249.4/44.99.74/8.853.40/2.000.35/0.23
Dogs 5/62.012.8/16.32.41/1.7426.7/16.15.26/3.170.595/0.7580.11/0.24
0.08400.0919Nhp 10.544.01.8135.57.952.070.26
Nhp 21.022.50.93019.24.301.060.25
Nhp 32.02.14N.S.6.071.360.1010.07
9-Hydroxyrisperidone0.203d0.0903eDogs 1/20.511.7/20.70.490/0.5507.68/5.741.63/1.220.223/0.3940.14/0.32
Dogs 3/41.066.3/35.11.36/2.2122.3/22.24.72/4.701.26/0.6680.27/0.14
Dogs 5/62.026.5/98.66.06/12.640.3/67.88.53/14.40.505/1.880.06/0.13
0.1850.105Nhp 10.581.42.3830.17.411.410.19
Nhp 21.01415.4238.99.582.450.26
Nhp 32.041.7N.S.68.816.90.7240.04
0.17 (0.12, 0.22)f
  • N.S., no sample.

  • a t corresponds to the euthanasia time postdose.

  • b Observed Cb,u (Cb,u,obs) was calculated by eq. 5 (Materials and Methods).

  • c Predicted Cb,u (Cb,u,pred) was calculated by eq. 6 (Materials and Methods).

  • d Values were reported by Mannens et al. (1994).

  • e Dog fu,b was not determined. Thus, the mean of the experimentally determined rat and nhp fu,b values was used for the calculation of Cb,u,obs.

  • f Estimated mean and corresponding 95% CI for Cb,u,pred/Cb,u,obs.