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Cited by 79Parkinson's Disease Mechanisms and TreatmentsNeurological disorders and treatmentsNeurotransmitter Receptor Influence on Behavior

Diurnal motor variations to repeated doses of levodopa in Parkinson's disease

Bonuccelli, Ubaldo, Del Dotto, Paolo, Lucetti, Claudio, Petrozzi, Lucia, Bernardini, Silvia, Gambaccini, Gianna, Rossi, Giuseppe, Piccini, Paola·2000·Clinical Neuropharmacology
DOI 10.1097/00002826-200001000-00006
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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 significant 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.

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Crossref · 10.1097/00002826-200001000-00006

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  • Many symptoms and signs associated with Parkinson's disease demonstrate diurnal variations in intensity and frequency.

    “Many symptoms and signs associated with PD demonstrate diurnal variations in its intensity and frequency.”

    From Circadian dysregulation in Parkinson's disease (2017) · cites this paper as Bonuccelli et al., 2000

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Authors
Bonuccelli, U., Del Dotto, P., Lucetti, C., Petrozzi, L., Bernardini, S., Gambaccini, G., Rossi, G., & Piccini, P.
Affiliations
University of Pisa (IT)
Corresponding author
Bonuccelli, Ubaldo
ORCID
Venue
Clinical Neuropharmacology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2000-01
Volume
23
Issue
1
Pages
28-33
ISSN
0362-5664 (ISSN-L)
DOI
10.1097/00002826-200001000-00006
OpenAlex
W2095239618
Cited by
79
References
21
Citations by year
2026: 3 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 3 · 2014: 4 · 2013: 1 · 2012: 2
FWCI
0.68
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
Parkinson's disease, levodopa, diurnal variation, motor symptoms, wearing-off phenomenon, 3-O-methyldopa, levodopa pharmacokinetics, levodopa/carbidopa, de novo Parkinson's disease
MeSH terms
Administration, Oral, Antiparkinson Agents, Circadian Rhythm, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Levodopa, Male, Middle Aged, Motor Activity, Parkinson Disease, Psychomotor Performance, Tremor, Tyrosine, Walking

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