The population pharmacokinetics of pramipexole in Parkinson's disease patients

Pramipexole(PPX) is a synthetic amino-benzathiazole derivative dopamine agonist in Phase III development as a new treatment for Parkinson's Disease. The population pharmacokinetics(PK) of PPX were evaluated in 468 patients with 1039 concentrations from 3 Phase III trials using NONMEM. The mean (±SD) age and creatinine clearance (CrCL) were 62 (±10) years and 73.1 (±20.5) mg/dL. The data were best fit by a one compartment model with first order absorption. The regression model for PPX CL was CL (mL/min) = 209 + 2.88(CrCL -25.6). CL was 12.7% lower for females, 28.5% higher for blacks, and 16.7% higher in other non-white patients. The co-administration of amantadine resulted in a 9.0% decrease in PPX CL and the co-administraton of other drugs renally secreted by the cationic transport system decreased PPX CL by 17.7%. The absorption rate constant (Ka) was estimated to be 1.1 (1/hr) and the volume of distribution(Vd) was estimated to be 430 (L). The interindividual variability of CL was 21.2 %CV. The residual variability was 19.2%CV. Due to recommended dose titration schedules these findings do not warrant a priori dose adustments.