Repeated levodopa infusions in fluctuating Parkinson's disease: clinical and pharmacokinetic data.

The short-term efficacy of continuous intravenous infusions of levodopa (with oral peripheral decarboxylase inhibitor) in abolishing or reducing "on-off" fluctuations in patients with Parkinson's disease is well established. However, there are suggestions that clinical response may be less good with longer infusions, or infusions on consecutive days. We therefore gave intravenous infusions of levodopa to three such subjects on five consecutive days (6 h on day 1, 12 h/day on days 2 to 5). One subject's symptoms were perfectly controlled, one experienced one "off" period per day, and the third developed one or two off-periods per day. Nevertheless, clinical control in all three subjects was superior with levodopa infusions to that seen on optimum oral therapy. Plasma levodopa concentrations during the infusions could be correlated with off to on, and with on to off switches. In general, subjects needed higher plasma levodopa levels to turn "on" than to keep them mobile once on, and the threshold levels below which off-periods supervened were lower still. These experiments show that repeated intravenous infusions of levodopa are very effective in some parkinsonian subjects, who may be suitable candidates for prolonged parenteral treatment with alternative, more highly soluble, dopaminergic drugs.