Levodopa pharmacokinetic mechanisms and motor fluctuations in Parkinson's disease

Levodopa pharmacokinetic mechanisms and motor fluctuations in Parkinson's disease The contribution of the peripheral and central pharmacokinetic mechanisms of levodopa to the pathogenesis of the motor fluctuations that complicate its long‐term administration was studied in 28 parkinsonian patients. The rate of levodopa clearance from the general circulation, its plasma half‐life, and apparent volume of distribution were indistinguishable between patients with the on‐off or the wearing‐off phenomenon and those with a stable response to levodopa or those who had not been previously treated with levodopa. Peripheral pharmacokinetic factors are thus unlikely to account for the development of these response fluctuations. Conversely, the efficacy half‐time of levodopa differed markedly among the four response groups studied and may provide a quantitative index of central mechanisms that favor the development of the wearing‐off and on‐off phemonena. Although symptom duration was the best predictor of the severity of untreated parkinsonism, levodopa dose correlated best with response half‐time. The wearing‐off phenomenon may primarily reflect the loss of buffering capacity caused by degeneration of the dopamine neurons, while the development of the on‐off phenomenon appears to require additional postsynaptic changes, possibly at the receptor level. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Neurology Wiley

Levodopa pharmacokinetic mechanisms and motor fluctuations in Parkinson's disease

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Publisher
Wiley
Copyright
Copyright © 1987 American Neurological Association
ISSN
0364-5134
eISSN
1531-8249
DOI
10.1002/ana.410210409
pmid
3579222
Publisher site
See Article on Publisher Site

Abstract

The contribution of the peripheral and central pharmacokinetic mechanisms of levodopa to the pathogenesis of the motor fluctuations that complicate its long‐term administration was studied in 28 parkinsonian patients. The rate of levodopa clearance from the general circulation, its plasma half‐life, and apparent volume of distribution were indistinguishable between patients with the on‐off or the wearing‐off phenomenon and those with a stable response to levodopa or those who had not been previously treated with levodopa. Peripheral pharmacokinetic factors are thus unlikely to account for the development of these response fluctuations. Conversely, the efficacy half‐time of levodopa differed markedly among the four response groups studied and may provide a quantitative index of central mechanisms that favor the development of the wearing‐off and on‐off phemonena. Although symptom duration was the best predictor of the severity of untreated parkinsonism, levodopa dose correlated best with response half‐time. The wearing‐off phenomenon may primarily reflect the loss of buffering capacity caused by degeneration of the dopamine neurons, while the development of the on‐off phenomenon appears to require additional postsynaptic changes, possibly at the receptor level.

Journal

Annals of NeurologyWiley

Published: Apr 1, 1987

References

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