Duodenal and gastric delivery of levodopa in parkinsonism.
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.
Kurlan
R
R
Department of Neurology, University of Rochester School of Medicine and Dentistry, NY 14642.
Nutt
J G
JG
Woodward
W R
WR
Rothfield
K
K
Lichter
D
D
Miller
C
C
Carter
J H
JH
Shoulson
I
I
D000284:Administration, Oral; D004334:Drug Administration Schedule; D004386:Duodenum; D005746:Gastric Emptying; D006801:Humans; D007263:Infusions, Parenteral; D007980:Levodopa / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy*; D013270:Stomach
D007980:Levodopa