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The long-duration response to L-dopa in the treatment of early PD

From the Institute of Neurology (Drs. Zappia, Bosco, Oliveri, Gambardella, and Quattrone), University of Catanzaro; and the Institute of Experimental Medicine and Biotechnology (Drs. Nicoletti, Branca, Oliveri, Caracciolo, Napoli, Gambardella, and Quattrone), National Research Council, Piano Lago di Mangone (Cosenza), Italy.

Address correspondence and reprint requests to Prof. Aldo Quattrone, Clinica Neurologica, Facoltà di Medicina, Via T. Campanella, 88100 Catanzaro, Italy; e-mail: quattrone.unicz{at}interbusiness.it

OBJECTIVE: To investigate the long-duration response (LDR) to L-dopa resulting from different regimens of L-dopa.

BACKGROUND: In clinical practice, L-dopa is usually administered without considering the LDR due to the drug. Moreover, it has not been established whether in early PD a multiple daily intake of small doses of L-dopa may induce a sustained LDR.

METHODS: Twenty-four patients with early PD underwent a double-blind, crossover trial, comparing three different 15-day treatment periods with L-dopa: treatment A (250 mg every 24 hours); treatment B (250 mg every 8 hours); and treatment C (125 mg every 8 hours). After completion, 20 patients underwent a subsequent open-label randomized trial with prolonged treatments (250 mg every 24 hours or 125 mg every 8 hours) up to 3 months. LDR was measured at the end of each treatment.

RESULTS: All patients achieved a sustained LDR after treatments A and B, whereas only 17% of patients reached a sustained LDR after treatment C. Overall, the LDRs resulting from treatments A and B had similar magnitude and were larger than the LDR deriving from treatment C. After 3 months of prolonged treatments, only three of 10 patients treated with 125 mg every 8 hours increased their LDR, whereas all 10 patients treated with 250 mg every 24 hours had a maximal and stable LDR.

CONCLUSIONS: Sustained LDR to L-dopa is dependent on the amount of the single doses of the drug. A regimen scheduling small, divided doses during the day, as done in clinical practice, is a questionable therapy for the achievement of a sustained LDR.

Key words: PD—L-dopa—Long-duration response—Pharmacodynamics—Movement time.

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