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On-off fluctuations in Parkinson's disease. A clinical and neuropharmacological study.

On-off fluctuations have been studied in twenty patients with Parkinson's disease on long-term levodopa treatment. The pattern of fluctuations was related to the timing of oral levodopa ingestion in all patients. 'Predictable' fluctuators were characterized by fewer daily doses taken at longer intervals than 'unpredictable' fluctuators in whom individual dose responses tended to overlap. Most patients at least once a day experienced an unexplained failure of an oral dose to take effect. Administration of levodopa by intravenous infusion at a constant rate brought about a dramatic extension in the duration of mobility and reduced the frequency of fluctuations compared with oral therapy; apomorphine consistently reversed off phases when administered shortly after their onset, whereas lisuride was less often effective. We conclude that the development of a sustained-release formulation of levodopa would lead to improved control of the response fluctuations seen with conventional levodopa preparations.