Gastrointestinal barriers to levodopa transport and absorption in Parkinson's disease

International Parkinson and Movement Disorders Society Non-Motor Parkinson's Disease Study Group

doi:10.1111/ene.15734

Gastrointestinal barriers to levodopa transport and absorption in Parkinson's disease

International Parkinson and Movement Disorders Society Non-Motor Parkinson's Disease Study Group

Research output: Contribution to journal › Review article › peer-review

28 Citations (Scopus)

Abstract

Levodopa is the gold standard for the symptomatic treatment of Parkinson's disease (PD). There are well documented motor and non-motor fluctuations, however, that occur almost inevitably once levodopa is started after a variable period in people with PD. Whilst brain neurodegenerative processes play a part in the pathogenesis of these fluctuations, a range of barriers across the gastrointestinal (GI) tract can alter levodopa pharmacokinetics, ultimately contributing to non-optimal levodopa response and symptoms fluctuations. GI barriers to levodopa transport and absorption include dysphagia, delayed gastric emptying, constipation, Helicobacter pylori infection, small intestinal bacterial overgrowth and gut dysbiosis. In addition, a protein-rich diet and concomitant medication intake can further alter levodopa pharmacokinetics. This can result in unpredictable or sub-optimal levodopa response, ‘delayed on’ or ‘no on’ phenomena. In this narrative review, we provided an overview on the plethora of GI obstacles to levodopa transport and absorption in PD and their implications on levodopa pharmacokinetics and development of motor fluctuations. In addition, management strategies to address GI dysfunction in PD are highlighted, including use of non-oral therapies to bypass the GI tract.

Original language	English
Pages (from-to)	1465-1480
Number of pages	16
Journal	European Journal of Neurology
Volume	30
Issue number	5
Early online date	9 Feb 2023
DOIs	https://doi.org/10.1111/ene.15734
Publication status	Published - May 2023

Keywords

absorption
constipation
delayed gastric emptying
diet
dysphagia
levodopa
medication
microbiota
Parkinson's disease
pharmacokinetics
transport

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10.1111/ene.15734

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title = "Gastrointestinal barriers to levodopa transport and absorption in Parkinson's disease",

abstract = "Levodopa is the gold standard for the symptomatic treatment of Parkinson's disease (PD). There are well documented motor and non-motor fluctuations, however, that occur almost inevitably once levodopa is started after a variable period in people with PD. Whilst brain neurodegenerative processes play a part in the pathogenesis of these fluctuations, a range of barriers across the gastrointestinal (GI) tract can alter levodopa pharmacokinetics, ultimately contributing to non-optimal levodopa response and symptoms fluctuations. GI barriers to levodopa transport and absorption include dysphagia, delayed gastric emptying, constipation, Helicobacter pylori infection, small intestinal bacterial overgrowth and gut dysbiosis. In addition, a protein-rich diet and concomitant medication intake can further alter levodopa pharmacokinetics. This can result in unpredictable or sub-optimal levodopa response, {\textquoteleft}delayed on{\textquoteright} or {\textquoteleft}no on{\textquoteright} phenomena. In this narrative review, we provided an overview on the plethora of GI obstacles to levodopa transport and absorption in PD and their implications on levodopa pharmacokinetics and development of motor fluctuations. In addition, management strategies to address GI dysfunction in PD are highlighted, including use of non-oral therapies to bypass the GI tract.",

keywords = "absorption, constipation, delayed gastric emptying, diet, dysphagia, levodopa, medication, microbiota, Parkinson's disease, pharmacokinetics, transport",

author = "{International Parkinson and Movement Disorders Society Non-Motor Parkinson's Disease Study Group} and Valentina Leta and Lisa Klingelhoefer and Katherine Longardner and Marta Campagnolo and Levent, {Hafize {\c C}otur} and Federico Aureli and Vinod Metta and Roongroj Bhidayasiri and Guy Chung-Faye and Cristian Falup-Pecurariu and Fabrizio Stocchi and Peter Jenner and Tobias Warnecke and K. Ray Chaudhuri",

note = "Funding Information: The views expressed are those of the authors and not necessarily those of the NHS, NIHR or Department of Health. The authors acknowledge the support of the IP‐MDS Non‐Motor Parkinson's Disease Study Group, the NIHR London South CRN Network and the NIHR BRC. This article represents independent collaborative research part funded by the NIHR BRC at South London and Maudsley NHS Foundation Trust and KCL. Figures 1, 2, 3 and S1 were created with BioRender.com. Publisher Copyright: {\textcopyright} 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.",

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AU - International Parkinson and Movement Disorders Society Non-Motor Parkinson's Disease Study Group

AU - Leta, Valentina

AU - Klingelhoefer, Lisa

AU - Longardner, Katherine

AU - Campagnolo, Marta

AU - Levent, Hafize Çotur

AU - Aureli, Federico

AU - Metta, Vinod

AU - Bhidayasiri, Roongroj

AU - Chung-Faye, Guy

AU - Falup-Pecurariu, Cristian

AU - Stocchi, Fabrizio

AU - Jenner, Peter

AU - Warnecke, Tobias

AU - Ray Chaudhuri, K.

N1 - Funding Information: The views expressed are those of the authors and not necessarily those of the NHS, NIHR or Department of Health. The authors acknowledge the support of the IP‐MDS Non‐Motor Parkinson's Disease Study Group, the NIHR London South CRN Network and the NIHR BRC. This article represents independent collaborative research part funded by the NIHR BRC at South London and Maudsley NHS Foundation Trust and KCL. Figures 1, 2, 3 and S1 were created with BioRender.com. Publisher Copyright: © 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

PY - 2023/5

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N2 - Levodopa is the gold standard for the symptomatic treatment of Parkinson's disease (PD). There are well documented motor and non-motor fluctuations, however, that occur almost inevitably once levodopa is started after a variable period in people with PD. Whilst brain neurodegenerative processes play a part in the pathogenesis of these fluctuations, a range of barriers across the gastrointestinal (GI) tract can alter levodopa pharmacokinetics, ultimately contributing to non-optimal levodopa response and symptoms fluctuations. GI barriers to levodopa transport and absorption include dysphagia, delayed gastric emptying, constipation, Helicobacter pylori infection, small intestinal bacterial overgrowth and gut dysbiosis. In addition, a protein-rich diet and concomitant medication intake can further alter levodopa pharmacokinetics. This can result in unpredictable or sub-optimal levodopa response, ‘delayed on’ or ‘no on’ phenomena. In this narrative review, we provided an overview on the plethora of GI obstacles to levodopa transport and absorption in PD and their implications on levodopa pharmacokinetics and development of motor fluctuations. In addition, management strategies to address GI dysfunction in PD are highlighted, including use of non-oral therapies to bypass the GI tract.

AB - Levodopa is the gold standard for the symptomatic treatment of Parkinson's disease (PD). There are well documented motor and non-motor fluctuations, however, that occur almost inevitably once levodopa is started after a variable period in people with PD. Whilst brain neurodegenerative processes play a part in the pathogenesis of these fluctuations, a range of barriers across the gastrointestinal (GI) tract can alter levodopa pharmacokinetics, ultimately contributing to non-optimal levodopa response and symptoms fluctuations. GI barriers to levodopa transport and absorption include dysphagia, delayed gastric emptying, constipation, Helicobacter pylori infection, small intestinal bacterial overgrowth and gut dysbiosis. In addition, a protein-rich diet and concomitant medication intake can further alter levodopa pharmacokinetics. This can result in unpredictable or sub-optimal levodopa response, ‘delayed on’ or ‘no on’ phenomena. In this narrative review, we provided an overview on the plethora of GI obstacles to levodopa transport and absorption in PD and their implications on levodopa pharmacokinetics and development of motor fluctuations. In addition, management strategies to address GI dysfunction in PD are highlighted, including use of non-oral therapies to bypass the GI tract.

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KW - constipation

KW - delayed gastric emptying

KW - diet

KW - dysphagia

KW - levodopa

KW - medication

KW - microbiota

KW - Parkinson's disease

KW - pharmacokinetics

KW - transport

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DO - 10.1111/ene.15734

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C2 - 36757008

AN - SCOPUS:85150523936

SN - 1351-5101

VL - 30

SP - 1465

EP - 1480

JO - European Journal of Neurology

JF - European Journal of Neurology

IS - 5

ER -

Gastrointestinal barriers to levodopa transport and absorption in Parkinson's disease

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