A levodopa kinetic-dynamic study of the rate of progression in Parkinson's disease

Objective: The aims of the study were to follow prospectively the intrasubject progression of idiopathic PD in a cohort of patients using levodopa kinetic-dynamic modeling and to assess the relation between the rate of progression of the disease and patients' different clinical characteristics. Methods: Thirty-four patients (Hoehn and Yahr stages 1 to 3) enrolled in the longitudinal follow-up. Each patient was examined at 1-year intervals over a median 4 years by a standardized oral levodopa test. The primary measure outcome was the computed half-life of levodopa in the 'effect compartment' (t1/2(eq)), a proposed indicator of nigrostriatal dopaminergic functionality and integrity. Results: Values of levodopa t1/2(eq) correlated negatively with severity of symptoms (r = -0.652, p <0.0001) and decreased over the years together with a worsening of patients' clinical stage (p <0.001). The rate of reduction in drug t1/2(eq) was more rapid in patients at the earlier stages of the disease compared with the more advanced ones, falling from a median annual reduction of 37 minutes in patients at initial Hoehn and Yahr stage 1 to 6.5 minutes in stage 3 patients (p <0.001). Patients without tremor at onset, otherwise comparable to patients with tremor for baseline values of levodopa t1/2(eq), disease severity, duration, and daily dose of levodopa, tended to show a higher rate of reduction in levodopa t1/2(eq) than patients with tremor. Overall, patients' annual reduction in levodopa t1/2(eq) over baseline values averaged 17 ± 9%. Conclusions: These results are in keeping with PET findings on the objective assessment of idiopathic parkinsonism evolution, and they support the suggestion that levodopa pharmacodynamic modeling may offer a practical clinical tool to assess indirectly the functional integrity of the nigrostriatal dopaminergic system over time in parkinsonian patients.