Does tolerance develop to levodopa? Comparison of 2- and 21-H levodopa infusions.

To determine if acute tolerance to levodopa develops, we compared the response to 2- and 21-h levodopa infusions with the rate adjusted during the long infusion to yield the same plasma concentration as at the end of the 2-h infusion. The duration of response after discontinuing the long infusions was briefer than after discontinuing the short infusion, suggesting the development of tolerance. Furthermore, dyskinesia severity was greater during long infusions. We conclude that continuous dopaminergic stimulation with levodopa may not offer optimal control of parkinsonism in patients with response fluctuations.