The response to levodopa in parkinson's disease: Imposing pharmacological law and order


  • Dr John G. Nutt MD,

    Corresponding author
    1. Departments of Neurology and Pharmacology, Oregon Health Sciences University, Portland, New Zealand
    • Department of Neurology, L-226, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098
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  • Nicholas H. G. Holford MB, MRCP(Uk), FRACP

    1. Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand
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The seemingly unpredictable response to levodopa in patients with Parkinson's disease can be understood as an interaction between several distinct pharmacological effects of levodopa. The most important are a short-duration response with a half-life of minutes to hours and a long-duration response with a half-life of days, superimposed on diurnal motor variation. A negative response characterized by brief worsening before and after the short-duration response and dyskinesia accentuate the short-duration response. These various responses are modified by disease progression and long-term levodopa therapy. Pharmacodynamic modeling of the short-duration response indicates that with time, the response becomes less graded and small changes in levodopa concentrations can produce big changes in response. In this setting, unpredictability arises from the variation in absorption and distribution of levodopa.