Pharmacodynamics of the long-duration response to levodopa in PD

Objective: To determine the latency, magnitude, and duration of the long-duration response (LDR) to levodopa in PD in relationship to the administration of levodopa at different interdose intervals. Methods: In six patients with PD, two different 15-day treatment regimens were used in which the drug was administered with interdose intervals of 24 or 8 hours. Results: The LDR built up within a few days with either regimen, but a faster rate of administering levodopa shortened the latency to the appearance of a sustained LDR. Once a sustained response had been reached, the magnitude of the LDR showed a stable ceiling effect that was independent of the levodopa schedule. After discontinuation of treatment, the decay of the LDR was similar for both regimens. Conclusions: The system underlying the LDR to levodopa may be completely saturated when a sustained response has been fully developed. The intervals between doses of levodopa shorter than the interval effective to reach a sustained LDR should not be used in the clinical management of patients with PD because the antiparkinsonian benefit deriving from the LDR is already maximal and briefer intervals do not provide a greater benefit.