Motor fluctuations during continuous levodopa infusions in patients with Parkinson's disease

Movement Disorders : Official Journal of the Movement Disorder Society
J G NuttW R Woodward

Abstract

The cause of motor fluctuations occurring during constant-rate levodopa infusions is unknown. We examined whether known pharmacokinetic factors could explain the fluctuations and looked for clues to pharmacodynamic causes. Eleven subjects with stage III-V Parkinson's disease (PD) and a fluctuating response to levodopa underwent constant-rate infusions for 36-110 h. Levodopa, 3-O-methyldopa (3-OMD), and plasma large neutral amino acids (LNAAs) were measured at 2- to 6-h intervals and PD was monitored hourly from 07:00 to 22:00 h with tapping speed. Ten subjects had motor fluctuations during the infusions. Zero to 68% of the variability of tapping speed could be explained by variation in plasma LNAA concentrations in individual subjects. Fluctuations occurred more commonly later in the day, which may be related to the tendency for LNAAs to increase during the day. Motor fluctuations were not associated with minor variations in levodopa or 3-OMD concentrations. Fluctuations during constant infusions were more marked in patients using larger daily doses of oral levodopa; severity of PD did not predict fluctuations during the infusions. There was no trend for fluctuations or dyskinesia to decrease or increase during several days of ...Continue Reading

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Citations

Mar 29, 2002·Movement Disorders : Official Journal of the Movement Disorder Society·Azi H RajputOleh Hornykiewicz
Mar 24, 2004·Parkinsonism & Related Disorders·Nicolas SimonFrançois Viallet
May 4, 2004·Parkinsonism & Related Disorders·Ali H RajputOleh Hornykiewicz
Aug 8, 2001·Parkinsonism & Related Disorders·J G Nutt
Oct 29, 2000·Trends in Neurosciences·J G NuttF Stocchi
Feb 22, 2000·Clinical Neuropharmacology·U BonuccelliP Piccini
Aug 2, 2002·Clinical Neuropharmacology·Bernard Bruguerolle, Nicolas Simon
Dec 17, 2004·Clinical Neuropharmacology·Dag Nyholm, Sten-Magnus Aquilonius
May 25, 2011·Drug Design, Development and Therapy·Patrick Hickey, Mark Stacy
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Apr 13, 2012·Expert Opinion on Drug Discovery·Piera SozioAntonio Di Stefano
Apr 8, 2010·Chronobiology International·Audrey BoulameryBernard Bruguerolle
Jan 19, 2016·Frontiers in Pharmacology·Shan H SiddiqiKevin J Black
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Jan 3, 2012·Physiotherapy Canada. Physiothérapie Canada·Vanina Dal Bello-HaasAmy Metcalfe
Nov 28, 2017·Movement Disorders : Official Journal of the Movement Disorder Society·C Warren Olanow, Fabrizio Stocchi
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Sep 17, 2004·Movement Disorders : Official Journal of the Movement Disorder Society·C Warren OlanowFabrizio Stocchi
Mar 12, 2015·Movement Disorders : Official Journal of the Movement Disorder Society·John G Nutt
Sep 8, 2006·Movement Disorders : Official Journal of the Movement Disorder Society·John G Nutt
Sep 11, 2008·Movement Disorders : Official Journal of the Movement Disorder Society·C Warren Olanow
Sep 11, 2008·Movement Disorders : Official Journal of the Movement Disorder Society·John G Nutt
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