Longitudinal monitoring of the levodopa concentration-effect relationship in Parkinson's disease.
We prospectively evaluated over 4 years the intrasubject relationship between levodopa plasma concentration and the tapping effect after a standard oral levodopa test in 28 patients with mild-to-moderate idiopathic Parkinson's disease. The onset and duration of the tapping effect significantly shortened over years; response amplitude did not vary. Levodopa plasma kinetics remained unchanged. Pharmacodynamic modeling indicated a progressive decrease in the equilibration half-life between plasma drug concentration and effect, which correlated with the shorter motor response. No clear-cut change in maximum response (Emax) emerged, but levodopa concentration needed to yield 50% of maximum effect (EC50) significantly increased. These data indicate that the duration of motor response becomes a major determinant of drug efficacy over years. The modifications in levodopa effect-compartment equilibration half-life and EC50 further support the suggestion that alterations in cerebral levodopa kinetics have an important role in the development of response fluctuations.
Institute of Neurology, University of Bologna, Italy.
M
M
Contin
R
R
Riva
P
P
Martinelli
P
P
Cortelli
F
F
Albani
A
A
Baruzzi
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D007980:Levodopa / Q000097:blood* / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D008991:Monitoring, Physiologic; D009043:Motor Activity / Q000187:drug effects; D009994:Osmolar Concentration; D010300:Parkinson Disease / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D010919:Placebos
D010919:Placebos; D007980:Levodopa