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The Pharmacokinetics of L-DOPA in Plasma and CSF of the Monkey

  • John P. Hammerstad
  • William R. Woodward
  • Perry Gliessman
  • Brian Boucher
  • John G. Nutt
Part of the Advances in Behavioral Biology book series (ABBI, volume 39)

Abstract

L-DOPA is the single most effective therapeutic agent in the treatment of Parkinson’s disease (PD). After years of treatment, however, its efficacy is mitigated by the development of a fluctuating response (“on-off”) that may be as disabling as the disease. There are no changes in the peripheral pharmacokinetics of L-DOPA to explain the development of fluctuations1. Therefore, a change in the central pharmacokinetics or pharmacodynamics of L-DOPA and dopamine are postulated to underlie the appearance of fluctuations2–6. When a constant plasma concentration of L-DOPA is maintained by intravenous infusion in Parkinsonian patients, the motor fluctuations may be abolished for hours to days, indicating that the clinical response is dependant on the plasma level and that pharmacokinetic mechanisms contribute to the clinical fluctuations7. The short plasma half-life of L-DOPA and the regulation of its entry into brain by carrier-mediated transport may become critical factors when the decreased striatal storage of dopamine due to the loss of dopaminergic nerve terminals makes motor function dependant on the constant delivery of L-DOPA to striatum to support the continuous synthesis of dopamine8.

Keywords

Effective Therapeutic Agent Fluctuate Response Spinal Subarachnoid Space Brain Capillary Endothelium Cranial Compartment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • John P. Hammerstad
    • 1
    • 2
  • William R. Woodward
    • 1
    • 2
  • Perry Gliessman
    • 1
    • 2
  • Brian Boucher
    • 1
    • 2
  • John G. Nutt
    • 1
    • 2
  1. 1.Oregon Health Sciences UniversityPortlandUSA
  2. 2.Oregon Regional Primate Research CenterBeavertonUSA

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