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 Compound | Kp | fu,plasma | fu,brain | fu,brain,corrected | Vu,brain,pred | Kp,uu | Kp,uu,cyto,pred | Kp,uu,lyso,pred | Kp,uu,cell,pred |
|---|---|---|---|---|---|---|---|---|---|
| ml/g | |||||||||
| BIA 9-1079 | 0.0002 | 0.002 (0.001) | 0.008 (0.001) | 0.013 | 79.27 | 0.001 | 0.577 | 0.020 | 0.656 |
| Tolcapone | 0.0015 | 0.011 (0.003) | 0.162 (0.028) | 0.247 | 4.047 | 0.035 | 0.575 | 0.013 | 0.655 |
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.