Levodopa: pharmacology, pharmacokinetics, and pharmacodynamics.

The success of L-dopa therapy in patients with Parkinson's disease and the concepts discussed in this article are summarized in Figure 6. Even in advanced stages of disease, 80% of parkinsonian disability remains responsive to L-dopa therapy. The 50% of the response contaminated by response fluctuations should be viewed, at least in part, as a hopeful sign that the system is still responding to L-dopa therapy. Unfortunately suboptimal control of response fluctuations is still a source of consternation for patient and treating physicians alike. Response fluctuations notwithstanding, it should be emphasized that patients actually do better at every stage of disease for having been on L-dopa, as recently confirmed in a retrospective study of the relationship between response fluctuations and the timing of initiation of therapy. To the extent that the increasing frequency, amplitude, and complexity of response fluctuations add to the overall parkinsonian disability, the phenomenon demands a better understanding that will hopefully lead to better corrective or preventive measures.