title: 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 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.
authors.affiliation: Department of Biopharmaceutics and Pharmacokinetics, University of Uppsala, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Bredberg
authors.forename: D
authors.initials: D
authors.lastname: Nilsson
authors.forename: K
authors.initials: K
authors.lastname: Johansson
authors.forename: S M
authors.initials: SM
authors.lastname: Aquilonius
authors.forename: B
authors.initials: B
authors.lastname: Johnels
authors.forename: C
authors.initials: C
authors.lastname: Nyström
authors.forename: L
authors.initials: L
authors.lastname: Paalzow
mesh_terms: D000284:Administration, Oral; D000368:Aged; D002230:Carbidopa / Q000008:administration & dosage / Q000097:blood; D003102:Colloids; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D007441:Intubation, Gastrointestinal; D007980:Levodopa / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009048:Motor Skills / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D003102:Colloids; D007980:Levodopa; D002230:Carbidopa