Complicated response fluctuations in Parkinson's disease: response to intravenous infusion of levodopa

The cause(s) of response fluctuations in patients with Parkinson's disease treated chronically with levodopa is unknown. In some subjects it is difficult to establish a clear relation between levodopa dosage and timing and the resultant clinical effects. This may be due to variation in the degree of absorption of the drug, and in the latency from ingestion to peak plasma level and from plasma peak to central action. In one patient illustrated, careful analysis of "on-off" charts reveals an underlying pattern of end-of-dose deterioration at a time when history alone suggested a completely random response to levodopa. In three patients replacement of oral treatment by continuous intravenous infusion of levodopa, with oral administration of decarboxylase inhibitor, produced a prolonged and stable clinical response, even when ambulant. This response was maintained not only in one subject showing predictable fluctuations, but also in two subjects with unpredictable response to oral treatment. The addition of intravenous levodopa infusion to the usual oral regimen of the first patient when she was experiencing prolonged "off" periods despite generous doses of oral levodopa with decarboxylase inhibitor also produced stable clinical benefit. These results suggest that, even in patients with complicated response swings, central dopamine receptors remain available for stimulation providing levodopa can be delivered at a constant rate and in an adequate quantity to the brain.