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Optimizing Levodopa Pharmacokinetics: Intestinal Infusion Versus Oral Sustained-Release Tablets

Nyholm, Dag*; Askmark, Håkan*; Gomes–Trolin, Cecilia*; Knutson, Tina; Lennernäs, Hans; Nyström, Christer; Aquilonius, Sten-Magnus*

ORIGINAL ARTICLES
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Continuous duodenal infusion of carbidopa/levodopa has been shown to control motor fluctuations in advanced Parkinson's disease (PD). The authors compared the pharmacokinetics of levodopa and 3-O-methyldopa in patients with advanced PD after administration of an oral sustained-release levodopa preparation and after continuous intestinal levodopa infusion with a new formulation as a gel suspension. A randomized crossover trial was carried out in 12 patients. Carbidopa/levodopa was administered as an oral sustained-release tablet and by nasoduodenal continuous infusion for 3-week periods for each treatment. Plasma levodopa concentrations and motor performance were evaluated every 30 minutes during 3 test days of each treatment period. The average intraindividual coefficient of variation for the plasma levodopa concentrations after oral therapy was 34% and was significantly lower (14%, p < 0.01) during continuous infusion. Hourly video evaluations showed a significant increase in ON time during infusion and a significant decrease in OFF time and dyskinesia. Continuous intraduodenal delivery of a new carbidopa/levodopa formulation offers a means for markedly improved control of motor fluctuations in late stages of PD.

Departments of *Neuroscience, Neurology, †Surgery, and ‡Pharmacy, Uppsala University, Sweden

Supported in part by the Swedish Medical Research Council (grant no. 4373) and NeoPharma Production AB, Uppsala, Sweden.

Address correspondence and reprint requests to Dr. Dag Nyholm, Department of Neuroscience, Neurology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden; e-mail: dag.nyholm@neurologi.uu.se

© 2003 Lippincott Williams & Wilkins, Inc.