A wrinkle in ON-time - A GI structural abnormality confounding levodopa therapy with Duodopa rescue; a case study

Staisch, Julia; Bakis, Gennadiy; Nutt, John G.

doi:10.1016/j.parkreldis.2018.02.021

Cited by 5 publications

(3 citation statements)

References 5 publications

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“…Slow intestinal transit contributes to a delay, reduction or even blockage of oral levodopa uptake, with potential delay or loss of effect (see Figure S3) [40,92]. Slow transit constipation can, indeed, exacerbate delayed gastric emptying via a cologastric brake/reflex (rectal distension may inhibit gastric emptying via neural and humoral components) [93,94], prolong oral levodopa transportation time and increase the chances for levodopa to be prematurely metabolised by AADC and COMT in the GI tract [47].…”

Section: Con S Tipati Onmentioning

confidence: 99%

“…‘Outlet’ constipation, caused by anorectal dysfunction with defaecatory problems, occurs in up to twothirds of PwP but does not directly affect levodopa absorption and pharmacokinetics, respectively, although it can exacerbate slow transit constipation [3,18]. Slow intestinal transit contributes to a delay, reduction or even blockage of oral levodopa uptake, with potential delay or loss of effect (see Figure S3) [40,92]. Slow transit constipation can, indeed, exacerbate delayed gastric emptying via a cologastric brake/reflex (rectal distension may inhibit gastric emptying via neural and humoral components) [93,94], prolong oral levodopa transportation time and increase the chances for levodopa to be prematurely metabolised by AADC and COMT in the GI tract [47].…”

Section: Constipationmentioning

confidence: 99%

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

Leta

Klingelhoefer

Longardner

et al. 2023

Euro J of Neurology

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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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Section: Con S Tipati Onmentioning

confidence: 99%

Section: Constipationmentioning

confidence: 99%

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

Leta

Klingelhoefer

Longardner

et al. 2023

Euro J of Neurology

View full text Add to dashboard Cite

show abstract

“…These complications are characterized by dyskinesias and motor fluctuations or OFF periods, resulting in patients spending more time throughout the day with breakthrough PD symptoms, which may significantly reduce QoL and impair function [23]. Risk factors for motor complications identified in studies include PD severity, duration, and cumulative levodopa dose [21,22], but there is increasing recognition that PD-associated GI disorders also may delay, reduce, or block the absorption and uptake of oral levodopa, with potential delay or negation of its effects [1,[24][25][26]. Gastroparesis and alterations of the microbiome are present in animal models of PD utilizing rotenone [27] and MPTP [28].…”

Section: Introductionmentioning

confidence: 99%

Clinical implications of gastric complications on levodopa treatment in Parkinson's disease

Pfeiffer

Isaacson

Pahwa

2020

Parkinsonism & Related Disorders

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Disorders of the gastrointestinal (GI) tract are common and distressing nonmotor symptoms of Parkinson's disease (PD) that can adversely affect levodopa absorption and lead to OFF periods, also known as motor fluctuations. Gastroparesis, which is primarily defined as delayed gastric emptying (DGE), and Helicobacter pylori infection, which is present with increased frequency in PD, are among the most common and important GI disorders reported in PD that may impair oral levodopa absorption and increase OFF time. Symptoms of gastroparesis include nausea, vomiting, postprandial bloating, fullness, early satiety, abdominal pain, and weight loss. DGE has been reported in a substantial fraction of individuals with PD. Symptoms of H. pylori infection include gastritis and peptic ulcers. Studies have found that DGE and H. pylori infection are correlated with delayed peak levodopa plasma levels and increased incidence of motor fluctuations. Therapeutic strategies devised to minimize the potential that gastric complications will impair oral levodopa absorption and efficacy in PD patients include treatments that circumvent the GI tract, such as apomorphine injection, levodopa intestinal gel delivery, levodopa inhalation powder, and deep brain stimulation. Other strategies aim at improving gastric emptying in PD patients, primarily including prokinetic agents.

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Gastrointestinal dysfunction in the synucleinopathies

Chung

Pfeiffer

2020

Clin Auton Res

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A wrinkle in ON-time - A GI structural abnormality confounding levodopa therapy with Duodopa rescue; a case study

Cited by 5 publications

References 5 publications

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

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

Clinical implications of gastric complications on levodopa treatment in Parkinson's disease

Gastrointestinal dysfunction in the synucleinopathies

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