Table IV.
Population Brain Pharmacokinetic and Pharmacodynamic Parameter Estimates from Full and Reduced PBPKPD Model
| Parameter | Full model (FM) | Reduced model (RM) | % difference |
|---|---|---|---|
| Population mean (%RSE) | Population mean (%RSE) | ||
| CLbev(l/h/kg) | 0.433 (16) | 0.394 (15) | −10 |
| Kd (nM) | 14.6 (7) | 14.7 (8) | <1 |
| koff (h−1) | 3.04 (24) | 2.62 (24) | −16 |
| kon (nM−1 h−1)a | 0.208 | 0.178 | −17 |
| Proportional error (BC) | 0.479 (6) | 0.479 (6) | <1 |
| Additive error (D2RO) | 0.136 (5) | 0.136 (5) | <1 |
%RSE = Relative standard error as obtained from the COVARIANCE option in NONMEM
% difference calculated as 100-(Parameter estimate-RM*100/Parameter estimate-FM)
BC brain concentration; D 2 RO dopamine D2 receptor occupancy
akon derived as koff/Kd