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Pharmacokinetic behaviour of levodopa and 3-O-methyldopa after repeat administration of levodopa/carbidopa with and without entacapone in patients with Parkinson's disease.

Abstract
Addition of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) prolongs plasma metabolism of levodopa (LD). Objectives were to determine the clinical response after EN addition and the plasma degradation of LD and 3-O-methyldopa [3-OMD]. Not optimum treated hospitalised patients with Parkinson's disease received the same LD dosage on the first day only with carbidopa (CD) and on the second day with CD and EN (t.i.d.) within a standardised setting. We scored motor symptoms and measured LD- and 3-OMD levels on both days at fixed moments. Motor impairment significant better improved probably due to significant higher maximum concentrations [C(max)] and computed area under the curve values of LD levels during the LD/CD/EN condition. Time to C(max) of LD was significantly delayed after the first two LD/CD/EN intakes. An impact of EN on 3-OMD levels appeared. A possibly augmented LD absorption and a prolonged LD metabolism after EN supplementation may contribute to a more continuous LD delivery to the brain.
AuthorsT Müller, C Erdmann, S Muhlack, D Bremen, H Przuntek, O Goetze, D Woitalla
JournalJournal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 113 Issue 10 Pg. 1441-8 (Oct 2006) ISSN: 0300-9564 [Print] Austria
PMID16604302 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiparkinson Agents
  • Catechols
  • Nitriles
  • Tyrosine
  • Levodopa
  • entacapone
  • Carbidopa
  • 3-methoxytyrosine
Topics
  • Adult
  • Aged
  • Antiparkinson Agents (therapeutic use)
  • Area Under Curve
  • Carbidopa (therapeutic use)
  • Catechols (therapeutic use)
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Levodopa (pharmacokinetics, therapeutic use)
  • Male
  • Middle Aged
  • Motor Activity (drug effects)
  • Nitriles (therapeutic use)
  • Parkinson Disease (drug therapy)
  • Tyrosine (analogs & derivatives, pharmacokinetics, therapeutic use)

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