Intraduodenal infusion of a water-based levodopa dispersion for optimisation of the therapeutic effect in severe Parkinson's disease

Abstract

Motor performance of five patients with advanced Parkinson's disease was investigated during their optimum oral therapy (conventional tablets and/or depot capsules) and during a continuous duodenal infusion of levodopa. Due to the low water solubility of the drug, conventional tablets of levodopa + carbidopa (Sinemet^®) were milled and dispersed in a 1.8% aqueous methylcellulose solution. The dispersion was delivered nasoduodenally by a portable pump. The effect of levodopa in the two dosing regimens was estimated optico-electronically every 15 min and was also evaluated from videorecordings every 30 min and plasma levels of levodopa was regularly measured. Each dosage regimen the was studied twice, at a 2–4 day interval. Duodenal infusion improved motor function in all five patients and the fluctuations were reduced when compared to the oral therapy. Variation in plasma levodopa concentrations was 3–10 fold during oral therapy, while during the infusion a stable concentration was obtained. The therapeutic concentration varied from 0.3–3 μg ml⁻¹ between patients. The relative bioavailability of levodopa in the solid preparation compared to the dispersion was in all patients 100%. Our results encourage further development of a duodenal infusion system with a levodopa dispersion for clinical use in parkinsonian patients who show severe fluctuation.