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Longitudinal monitoring of the levodopa concentration-effect relationship in Parkinson's disease

Institute of Neurology, University of Bologna, Bologna, Italy.

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 (E_max) 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.

Address correspondence and reprint requests to Dr. Manuela Contin, Institute of Neurology, Via U. Foscolo 7, 40123 Bologna, Italy.

This work was part of the "Progetto Finalizzato Invecchiamento" of the National Research Council of Italy, grant number 932390.

Presented in part at the 45 th annual meeting of the American Academy of Neurology, New York, NY, April 1993.

Received November 16, 1993. Accepted in final form January 21, 1994.

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