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End-of-dose akinesia after a single intravenous infusion of the dopaminergic agonist piribedil in Parkinson's disease patients: A pharmacokinetic/pharmacodynamic, randomized, double-blind study

Authors

  • Nicolas Simon MD, PhD,

    1. Laboratoire de Pharmacologie Medicale et Clinique, Centre Hospitalier Universitaire Timone, Marseille, France
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  • Joëlle Micallef MD, PhD,

    1. CPCET, Centre Hospitalier Universitaire Timone, Institut des Neurosciences Cognitives de la Mediterran, CNRS-Universite de la Mediterranee, Marseille, France
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  • Jean-Charles Reynier MD,

    1. CPCET, Centre Hospitalier Universitaire Timone, Institut des Neurosciences Cognitives de la Mediterran, CNRS-Universite de la Mediterranee, Marseille, France
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  • Monique Lesourd MD,

    1. Institut de Recherches Internationales Servier, Courbevoie, France
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  • Tatiana Witjas MD,

    1. CPCET, Centre Hospitalier Universitaire Timone, Institut des Neurosciences Cognitives de la Mediterran, CNRS-Universite de la Mediterranee, Marseille, France
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  • André Alicherif MD, PhD,

    1. CPCET, Centre Hospitalier Universitaire Timone, Institut des Neurosciences Cognitives de la Mediterran, CNRS-Universite de la Mediterranee, Marseille, France
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  • Jean-Philippe Azulay MD, PhD,

    1. CPCET, Centre Hospitalier Universitaire Timone, Institut des Neurosciences Cognitives de la Mediterran, CNRS-Universite de la Mediterranee, Marseille, France
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  • Olivier Blin MD, PhD

    Corresponding author
    1. CPCET, Centre Hospitalier Universitaire Timone, Institut des Neurosciences Cognitives de la Mediterran, CNRS-Universite de la Mediterranee, Marseille, France
    • CPCET, CHU Timone, 264 rue St. Pierre, 13385 Marseille Cedex 5, France
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  • Presented at the annual meeting of the Movement Disorder Society, November 2002.

Abstract

This randomized, double-blind trial was designed to define the possible relationship between piribedil plasma concentrations and the decrease of the Unified Parkinson's Disease Rating Scale (UPDRS) motor score or the switch from off to on state after single intravenous infusion. Ten fluctuating patients with idiopathic Parkinson's disease (PD) received escalating doses of piribedil (2–16 mg) and placebo. Starting from 2 mg, piribedil was effective in reducing the motor deficit (UPDRS, motor score) including akinesia at the first evaluation time point of 15 minutes, and in reversing off state of 7 of 10 patients. The doses were equally effective, although the effect was more sustained with the highest dose of 16 mg. Piribedil was well tolerated up to a 16-mg dose and pharmacokinetics were linear up to the 16-mg dose. Plasma levels of piribedil were not correlated to the motor score improvement or switch from offon. In conclusion, a short single infusion of piribedil at 2 to 16 mg was safe and effective in improving motor symptoms, including akinesia, of fluctuating PD patients. © 2005 Movement Disorder Society

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