Levodopa peripheral pharmacokinetics and duration of motor response in Parkinson's disease.

  title={Levodopa peripheral pharmacokinetics and duration of motor response in Parkinson's disease.},
  author={P. A. Kempster and J. P. Frankel and M. Bovingdon and Roy A. Webster and Andrew John Lees and Gerald M. Stern},
  journal={Journal of Neurology, Neurosurgery \& Psychiatry},
  pages={718 - 723}
To assess the relative influence of central pharmacodynamic and peripheral pharmacokinetic factors on the duration of motor response to levodopa, the relationship between motor function and plasma levodopa levels was studied in 31 Parkinsonian patients. Duration of benefit from single levodopa doses while fasting depended on the degree to which the plasma levodopa level had declined over four hours; wearing off occurred when the plasma levodopa level had fallen to approximately 50% of peak… 

Pharmacokinetics and pharmacodynamics of levodopa

  • J. Nutt
  • Psychology, Medicine
    Movement disorders : official journal of the Movement Disorder Society
  • 2008
The pharmacokinetics and pharmacodynamics of levodopa are dominated by two features: the short plasma half‐life of the drug and the portion of the antiparkinsonian response that parallels the plasma

Effect of duration of levodopa/decarboxylase inhibitor therapy on the pharmacokinetic handling of levodopa in elderly patients with idiopathic Parkinson's disease

The amount by, and time for which, the plasma levodopa concentration exceeds any critical threshold for the competitive active uptake process into the brain may decrease with duration of therapy, which may explain in part the limited reversal of the neurological deficit.

Pharmacokinetic Optimisation in the Treatment of Parkinson’s Disease

  • D. Nyholm
  • Medicine, Biology
    Clinical pharmacokinetics
  • 2006
In general, initial dopamine receptor agonist monotherapy is associated with poorer motor performance and lower incidence of motor complications compared with levodopa, and CDS can be approached by optimising the use of dopaminergic drugs based on pharmacokinetic data.

The long duration response to levodopa in Parkinson's disease

Inferring the long duration response to levodopa in Parkinson's disease.

Motor response to levodopa in patients with parkinsonian motor fluctuations: a follow-up study over three years.

A short response time to the levodopa test dose was not an invariable finding in patients with severe fluctuations, whereas all had large response amplitudes and high "off" phase disability scores.

Diurnal differences in response to oral levodopa.

Results suggest that under controlled conditions which eliminated the effects of diet and overlapping levodopa effects the response to Levodopa remained unchanged throughout the day, and that the duration of response could be predicted by plasmalevodopa levels.

Concentration-Effect Relationship of Levodopa in Patients with Parkinson’s Disease

Findings support some current hypotheses on the origin of, and the pathophysiological process underlying, response fluctuations and there is some evidence that higher plasma concentrations of levodopa are required for similar motor effects when CR preparations are compared with IR preparations.

Effect of long-term therapy on the pharmacodynamics of levodopa. Relation to on-off phenomenon.

Dykinesia appeared before or with the antiparkinsonian effects in patients with stable responses, giving no indication of a higher threshold for dyskinesia in these patients compared with those with fluctuating responses.

Motor response to levodopa and the evolution of motor fluctuations in the first decade of treatment of Parkinson's disease

Comparison of test‐dose and pretreatment scores suggested that a substantial long‐duration response to levodopa remains after many years of treatment, and that lateralized motor deficits show a stronger long duration response than midline ones.



Peripheral pharmacokinetics of levodopa in untreated, stable, and fluctuating parkinsonian patients

The peripheral pharmacokinetics of levodopa do not differ between untreated, stable, and fluctuating patients, and that altered peripheral kinetics of the drug are unlikely to explain the development of the fluctuating state.

The "on-off" phenomenon in Parkinson's disease. Relation to levodopa absorption and transport.

Interference with absorption oflevodopa by food and by competition between large neutral amino acids and levodopa for transport from plasma to the brain may be partly responsible for the fluctuating clinical response in patients with Parkinson's disease.

Response to brief levodopa infusions in parkinsonian patients with and without motor fluctuations

The duration of improvement in tapping and walking speeds following discontinuation of 2-hour levodopa infusions in nine previously untreated (UT), seven stable (ST), and 17 fluctuating (FL) subjects did not support a reduced dopamine "storage capacity" as the sole explanation for the length of the short-duration response.

“On‐off” phenomenon with levodopa therapy in parkinsonism

  • S. Fahn
  • Psychology, Medicine
  • 1974
Serial half-hourly measurements of plasma levels of dopa, 3-O-methyldopa, and homovanillic acid showed partial concordance between clinical fluctuation and plasma dopa levels in patients receiving levodopa alone or in combination with carbidopa.

Asymmetry of substantia nigra neuronal loss in Parkinson's disease and its relevance to the mechanism of levodopa related motor fluctuations.

A pathological study of 21 patients with Parkinson's disease of asymmetrical onset revealed significant asymmetry of degeneration of the substantia nigra with greater neuronal loss contralateral to the initially affected body side, and suggested that striatal dopamine storage is not an important determinant of duration of clinical response to levodopa doses.

'On‐off' phenomenon in Parkinson's disease

Administration of a low-protein diet to parkinsonian patients with “on-off” syndromes consistently increased the total daily time of “on” states when compared with a high-protein diet. The clinical

Brain dopamine metabolism in patients with Parkinson's disease measured with positron emission tomography.

The capacity of the striatum to retain tracer was severely impaired in patients compared to controls and this may reflect a reduction of striatal dopamine storage in Parkinson's disease.

Aromatic L‐amino acid decarboxylase in rat corpus striatum

Findings indicate that after degeneration of dopaminergic terminals, striatal interneurons and efferent neurons, but not serotonergic terminals or glia, contain an important fraction of the residual AAAD.