Original ArticlesDiurnal Motor Variations to Repeated Doses of Levodopa in Parkinson's DiseaseBonuccelli, Ubaldo; Del Dotto, Paolo; Lucetti, Claudio; Petrozzi, Lucia; Bernardini, Silvia; Gambaccini, Gianna; Rossi, Giuseppe*; Piccini, Paola†Author Information Department of Neuroscience, University of Pisa; *Unit of Epidemiology and Biostatistics, Institute of Clinical Physiology, National Research Council, Pisa, Italy; and †Medical Research Council, Hammersmith Hospital, London, United Kingdom Address correspondence and reprint requests to Ubaldo Bonuccelli, Department of Neuroscience, University of Pisa, Via Roma 67, 56100 Pisa, Italy. Clinical Neuropharmacology: January-February 2000 - Volume 23 - Issue 1 - p 28-33 Buy Abstract Patients with Parkinson's disease (PD) in long-term levodopa therapy often complain of worsening of motor symptoms in the afternoon and evening. The pathophysiology of this phenomenon is not known. We evaluated the motor response to repeated doses of levodopa during a 12-hour period in 52 parkinsonian patients (19 de novo, 20 stable, and 13 wearing-off). On the day of the study, all patients received standard doses of levodopa/carbidopa at 8:00 a.m., 12:00 noon, and 4:00 p.m. Motor measurements such as tapping test, walking time, and tremor score, and blood samples for levodopa and 3-O-methyldopa (3OMD) plasma analysis, were performed hourly. Mean motor scores and pharmacokinetic data, evaluated for a period of 3 hours after each levodopa dose, were compared. In de novo patients, we did not observe diurnal changes in motor score, whereas a progressive daytime worsening was visible in stable and wearing-off patients. No significant difference in levodopa pharmacokinetics after each levodopa dose was observed within each patient group, whereas 3OMD plasma levels significantly increased with repeated levodopa administrations. However, no significant correlation between motor scores and 3OMD plasma levels was observed, suggesting that the diminishing motor response to afternoon and evening doses of levodopa in patients in long-term levodopa therapy does not relate to the pharmacokinetics of the drug. It is possible that this phenomenon may be an expression of the occurrence of tolerance to repeated doses of levodopa. © 2000 Lippincott Williams & Wilkins, Inc.