Pharmacokinetics of Levodopa in Patients With Parkinson Disease and Motor Fluctuations Depending on the Presence of Helicobacter pylori Infection

Narożańska, Ewa; Białecka, Monika; Adamiak-Giera, Urszula; Gawrońska-Szklarz, B; Sołtan, Witold; Schinwelski, Michał; Robowski, Piotr; Madalinski, Mariusz; Sławek, Jarosław

doi:10.1097/wnf.0000000000000037

Cited by 39 publications

(28 citation statements)

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“…They showed that the t max and C max were lower in HP negative patients while the AUC o was larger in the HP positive groups. They concluded that these differences may potentially have important clinical implications to the patient [24] . Their findings may thus help explain the significant differences in the baseline UPDRS and PDQ39 scores between our H. pylori - positive and negative patients.…”

Section: Discussionmentioning

confidence: 99%

Eradication of Helicobacter pylori Infection Improves Levodopa Action, Clinical Symptoms and Quality of Life in Patients with Parkinson's Disease

et al. 2014

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BackgroundPrevious studies have demonstrated a higher prevalence of Helicobacter pylori (H. pylori) infection in patients with Parkinson's disease (PD) compared to controls. H. pylori infection affects levodopa absorption and its eradication significantly improves clinical response to levodopa. Here, we studied the prevalence of H. pylori infection and its eradication effects among our PD patients.MethodsA prospective study involving idiopathic PD patients on levodopa therapy. 13C-urea breath test (UBT) was used to detect H. pylori. UBT-positive patients were given standard eradication therapy and followed up at 6 and 12 weeks in an open label single arm design. Repeat UBT was performed at 12 weeks. The UPDRS, PD NMQ, PD NMSS and PDQ-39 were administered at baseline and post-eradication (6 and 12 weeks). Levodopa ‘onset’ time and ON-duration were recorded.ResultsOf 82 patients recruited, 27 (32.9%) had positive UBT. H. pylori-positive patients had significantly poorer total UPDRS (p = 0.005) and PDQ39 (p<0.0001) scores compared to H. pylori-negative patients. At 12 weeks post-eradication, the mean levodopa onset time shortened by 14 minutes (p = 0.011). The mean ON duration time increased by 56 minutes at week 6 (p = 0.041) and 38 minutes at week 12 (p = 0.035). The total UPDRS scores (p<0.0001), scores for parts II (p = 0.001), III (p<0.0001) and IV (p = 0.009) were significantly better. The total PDQ-39 scores (p = 0.001) and subdomains mobility (p = 0.002), ADL (p = 0.001), emotional well being (p = 0.026) and stigma (p = 0.034) significantly improved. The PD NMSQ did not show significant improvement.Conclusions H. pylori eradication improved levodopa onset time, ON duration, motor severity and quality of life parameters. Screening and eradication of H. pylori is inexpensive and should be recommended in PD patients, particularly those with erratic response to levodopa.Trial RegistrationClinicalTrials.gov NCT02112812

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Section: Discussionmentioning

confidence: 99%

Eradication of Helicobacter pylori Infection Improves Levodopa Action, Clinical Symptoms and Quality of Life in Patients with Parkinson's Disease

et al. 2014

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“…Some investigations have reported that gastric Helicobacter pylori infection is a factor contributing to motor fluctuations, and that improvement in consistency of l ‐dopa effect occurs once the infection is eradicated . However, a recent study of l ‐dopa pharmacokinetics in PD patients both with and without Helicobacter pylori infection does not confirm that disposition of l ‐dopa is necessarily changed by presence of the infection . Another factor interfering with l ‐dopa uptake and associated with motor fluctuations is bacterial overgrowth occurring in the small intestine.…”

Section: L‐dopa Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

Levodopa therapy for Parkinson's disease: Pharmacokinetics and pharmacodynamics

2014

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For all its imperfections at treating Parkinson's disease (PD), orally-administered levodopa (l-dopa) can be regarded as the "platinum" standard of PD therapeutics for its impact on disability and discomfort and its cost-effectiveness. The past half-century has confirmed that the typical l-dopa-treated patient gains improvement for most Parkinsonian features, presumably by conversion of this amino acid into dopamine in the striatum. However, fundamental questions remain as to its full mechanism of action and how adverse reactions evolve. Various aspects of clinical phenomenology associated with chronic l-dopa use (such as dyskinesias and the long-duration anti-Parkinsonian response) present a continuing challenge for better understanding of its pharmacology. The pharmacokinetics of l-dopa tend to predict some of problems that can emerge during chronic therapy, which can be linked with its irregular uptake and marked dose-by-dose variability in plasma concentrations. Several new pharmaceutical approaches are targeted at the unique physiology of l-dopa uptake and are likely to improve the consistency of its anti-Parkinsonian effect.

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“…Remarkably, H. pylori uses levodopa in vitro as a growth supplement in an iron-restricted medium [ 34 ], suggesting H. pylori converts this phenylalanine/tyrosine derivative into a functional amino acid for its metabolism. Thus, the pharmacokinetics of levodopa may be altered by H. pylori , though the mechanism is not well understood [ 35 ].…”

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confidence: 99%

Stomaching the Possibility of a Pathogenic Role for Helicobacter pylori in Parkinson’s Disease

McGee

Disbrow

2018

JPD

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While a small subset of Parkinson’s disease cases have genetic causes, most cases are sporadic and may have an environmental contributor that has largely remained enigmatic. Remarkably, gastrointestinal symptoms in PD patients serve as a prodrome for the eventual motor dysfunctions. Herein, we review studies exploring a possible link between the gastric human pathogen Helicobacter pylori and PD. We provide plausible and testable hypotheses for how this organism might contribute to PD: 1) a toxin(s) produced by the bacteria; 2) disruption of the intestinal microbiome; 3) local inflammation that crosses the gut-brain axis, leading to neuroinflammation; and 4) manipulation of the pharmacokinetics of the PD drug levodopa by H. pylori, even in those not receiving exogenous levodopa. Key findings are: 1) people with PD are 1.5-3-fold more likely to be infected with H. pylori than people without PD; 2) H. pylori-infected PD patients display worse motor functions than H. pylori-negative PD patients; 3) eradication of H. pylori improves motor function in PD patients over PD patients whose H. pylori was not eradicated; and 4) eradication of H. pylori improves levodopa absorption in PD patients compared to that of PD patients whose H. pylori was not eradicated. Evidence is accumulating that H. pylori has a link with PD, but the mechanism is unclear. Future work should explore the effects of H. pylori on development of PD in defined PD animal models, focusing on the roles of H. pylori toxins, inflammation, levodopa absorption, and microbiome dysbiosis.

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Pharmacokinetics of Levodopa in Patients With Parkinson Disease and Motor Fluctuations Depending on the Presence of Helicobacter pylori Infection

Abstract: The H. pylori infection in PD patients with motor fluctuations, despite not significantly influencing PK parameters of LD and 3-OMD, may still have important clinical implications.

Cited by 39 publications

References 8 publications

Eradication of Helicobacter pylori Infection Improves Levodopa Action, Clinical Symptoms and Quality of Life in Patients with Parkinson's Disease

Eradication of Helicobacter pylori Infection Improves Levodopa Action, Clinical Symptoms and Quality of Life in Patients with Parkinson's Disease

Levodopa therapy for Parkinson's disease: Pharmacokinetics and pharmacodynamics

Stomaching the Possibility of a Pathogenic Role for Helicobacter pylori in Parkinson’s Disease

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