Pharmacokinetic and Pharmacodynamic Changes During the First Four Years of Levodopa Treatment in Parkinson’s Disease

摘要: The purpose of this analysis is to describe how levodopa pharmacokinetic and pharmacodynamic parameters change over the first 4 years long-term treatment in patients with Parkinson’s disease. Twenty previously untreated Parkinsonian were admitted general clinical research center (GCRC) for days at beginning therapy 6, 12, 24 48 months later. On each GCRC admission, received a 2 hr IV infusion on day 1 no oral between infusions. After admission treated dosed optimal control Parkinsonism. Motor function was measured by finger tapping rate. A pharmacokinetic–pharmacodynamic model incorporating 3 effect compartments used fit individual plasma concentrations rates. before (E01) improved 20 subsequently returned initial baseline start study. similar pattern seen motor second (E02) after withdrawal, decline predicted fall below study 6 years. Eight showed an increase maximum rate (Emax) approaching steady state 16 months. Ten Emax peak 31 One patient linear decrease another did not Longitudinal progress models time course Peak benefit, defined as difference E01 or E02 (Dmax1 Dmax2), increased particularly 3-day withdrawal. Deterioration pre-dose (E0) disease progresses coupled greater amplitude response due (Dmax) could be key factor contributing fluctuations associated treatment.