Duodenal and gastric delivery of levodopa in parkinsonism

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Abstract
To clarify the influence of gastric emptying on levodopa‐related motor fluctuations in Parkinson's disease, we assessed mobility and plasma levodopa concentrations in 10 patients during five modes of levodopa administration: (1) standard intermittent oral (SIO), (2) intermittent duodenal (ID), (3) continuous duodenal infusion (CDI), (4) continuous gastric infusion (CGI), and (5) controlled‐release Sinemet (CR‐4). The rank order from greatest to least for both percentage of time “on” and average mobility score was CDI, CGI, ID, CR‐4, and SIO. The rank order for variance of means, a measure of fluctuation, from least to greatest for mobility was CDI, CGI, CR‐4, ID, SIO, and for plasma levodopa concentrations was CDI, CGI, ID, SIO, and CR‐4. The results demonstrate that it is possible to produce very steady plasma concentrations of levodopa with a corresponding reduction in motor fluctuations by continuous intraduodenal administration of the drug. This mode of delivery is an ideal model for the development of optimal continuous‐release preparations of levodopa. Other enteral routes have produced a more variable plasma levodopa concentration and clinical response.