INTRADUODENAL INFUSION OF A WATER-BASED LEVODOPA DISPERSION FOR OPTIMIZATION OF THE THERAPEUTIC EFFECT IN SEVERE PARKINSONS-DISEASE

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(R)) 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 mug 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.