Pharmacokinetic parameters and binding data of BIA 9-1079 and tolcapone in plasma and brain after intravenous administration (10 mg/kg) to Wistar rats

The presented Vu,bram,pred, Kp,uu,cyto,pred, Kp,uu,lyso,pred, and Kp,uu,ceii,pred values were predicted according to the pH partitioning theory. The fu,plasma and fu,brain values are expressed as mean (S.D.), n = 4.

Test CompoundKpfu,plasmafu,brainfu,brain,correctedVu,brain,predKp,uuKp,uu,cyto,predKp,uu,lyso,predKp,uu,cell,pred
BIA 9-10790.00020.002 (0.001)0.008 (0.001)0.01379.270.0010.5770.0200.656
Tolcapone0.00150.011 (0.003)0.162 (0.028)0.2474.0470.0350.5750.0130.655
  • fu,plasma, unbound drug fraction in plasma; Kp, ratio of total brain-to-plasma AUC0-t; Kp,uu, unbound brain-to-plasma ratio; Kp,uu,cell,pred, predicted unbound drug intracellular-to-extracellular partitioning coefficient; Kp,uu,cyto,pred, predicted unbound cytosolic-to-extracellular drug concentration ratio; Kp,uu,lyso,pred, predicted lysosomic-to-cytosolic unbound drug concentration ratio; Vu,brain,pred, predicted volume of distribution of unbound drug in the brain.