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

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...

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Bibliographic Details
Published in:European journal of neurology Vol. 30; no. 5; pp. 1465 - 1480
Main Authors: Leta, Valentina, Klingelhoefer, Lisa, Longardner, Katherine, Campagnolo, Marta, Levent, Hafize Çotur, Aureli, Federico, Metta, Vinod, Bhidayasiri, Roongroj, Chung‐Faye, Guy, Falup‐Pecurariu, Cristian, Stocchi, Fabrizio, Jenner, Peter, Warnecke, Tobias, Ray Chaudhuri, K.
Format: Journal Article
Language:English
Published: England John Wiley & Sons, Inc 01.05.2023
Subjects:
Absorption
Antiparkinson Agents - therapeutic use
Constipation
delayed gastric emptying
diet
Dysbacteriosis
Dysphagia
Fluctuations
Gastric emptying
Gastrointestinal Tract
Helicobacter Infections - complications
Helicobacter Infections - drug therapy
Helicobacter pylori
Humans
Levodopa
Levodopa - adverse effects
Medical treatment
medication
microbiota
Movement disorders
Neurodegenerative diseases
Parkinson Disease - complications
Parkinson's disease
Pathogenesis
Pharmacokinetics
Signs and symptoms
Small intestine
transport
constipation
microbiota
Parkinson's disease
absorption
levodopa
delayed gastric emptying
dysphagia
pharmacokinetics
medication
diet
transport
ISSN:1351-5101, 1468-1331, 1468-1331
Online Access:Get full text
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Summary: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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ISSN:1351-5101
1468-1331
1468-1331
DOI:10.1111/ene.15734