Elevation of total homocysteine levels in patients with Parkinson’s disease treated with duodenal levodopa/carbidopa gel

  title={Elevation of total homocysteine levels in patients with Parkinson’s disease treated with duodenal levodopa/carbidopa gel},
  author={Thomas M{\"u}ller and Constanze Jugel and Reinhard Ehret and Georg Ebersbach and Gunar Bengel and Siegfried Muhlack and Fabian Klostermann},
  journal={Journal of Neural Transmission},
Levodopa/carbidopa (LD/CD) application elevates total plasma homocysteine (thcys). We determined thcys-, LD- and 3-O-methyldopa (3-OMD) concentrations in 28 patients with Parkinson’s disease (PD) on a LD/CD duodenal gel treatment. We found a distinct thcys increase (29.52 ± 28.98 μmol/l [median ± SD]) above the 15 μmol/l threshold and a significant (R = 0.7) correlation between LD and 3-OMD. thcys ascent was observed in relation with the onset of atherosclerosis, non-motor symptoms and… 

Elevated homocysteine levels in levodopa‐treated idiopathic Parkinson's disease: a meta‐analysis

L‐dopa treatment is associated with the increase in plasma Hcy level in patients with PD, and catechol‐O‐methyltransferase inhibitor (COMT‐I) may attenuate L‐ dopa‐induced elevation of Hcylevel.

Inhibition of catechol-O-methyltransferase modifies acute homocysteine rise during repeated levodopa application in patients with Parkinson’s disease

Levels of homocysteine in plasma after reiterated oral levodopa/DDI administration with and without the COMT-inhibitor entacapone (EN) are measured to consider acute repeated levodOPA/ DDI applications, as homocy steine and metabolically related 3-O-methyldopa accumulate due to their long plasma half-life in contrast to short-living levdopa.

The Effect of Hyperhomocysteinemia on Motor Symptoms, Cognitive Status, and Vascular Risk in Patients with Parkinson's Disease

There was no correlation between HHcy and the stage of the disease, severity of motor symptoms, cognitive status as assessed by the MMSE, vascular risk factors, carotid artery atherosclerotic findings, and ischemic brain lesions.

Continuous intestinal infusion of levodopa/carbidopa in advanced Parkinson's disease: efficacy, safety and patient selection.

An algorithm is proposed to help clinicians select the most suitable treatment option for patients with advanced Parkinson's disease, and there are three therapeutic options available for the management of patients at this advanced stage.

Necessity of long‐term alertness in levodopa‐carbidopa intestinal gel infusion for PD patients

Levodopa/carbidopa intestinal gel is a treatment for Parkinson’s disease patients with motor fluctuations refractory to conventional drug therapy and during chronic treatment several SAEs are seen, strongly reducing quality of life or life threatening.

Clinical significance of homocysteine (hcy) on dementia in Parkinson's disease (PD).

Motor complications, levodopa metabolism and progression of Parkinson's disease

  • T. Müller
  • Biology, Medicine
    Expert opinion on drug metabolism & toxicology
  • 2011
The author suggests that the future ‘ideal’ oral LD therapy should be homocysteine-reducing, methyl-group-donating, oxidative-stress-decreasing and antiglutamatergic while also allowing continuous delivery to the brain.

Malnutritional neuropathy under intestinal levodopa infusion

It is assumed that LCIG can provoke PNP most likely of malnutritional origin, and the assessment of predisposing factors before treatment as well as neurophysiological and laboratory screenings appear necessary.

Levodopa-carbidopa enteral suspension in advanced Parkinson’s disease: clinical evidence and experience

There are also observations that LCIG may be effective treatment for nonmotor symptoms (NMS although the evidence is limited, and there is a need for further research on the efficacy of LCIG in reducing NMS, dyskinesia and improving QoL.



Homocysteine levels after acute levodopa intake in patients with Parkinson's disease

  • T. MüllerW. Kuhn
  • Medicine, Biology
    Movement disorders : official journal of the Movement Disorder Society
  • 2009
L‐dopa metabolism is an important component for homocysteine elevation after one time L‐dop/DDI administration in PD patients with different L‐ dopa metabolism.

Acute homocysteine rise after repeated levodopa application in patients with Parkinson's disease.

Levodopa and 3-OMD levels in Parkinson patients treated with Duodopa

Role of homocysteine in the treatment of Parkinson's disease

  • T. Müller
  • Biology, Medicine
    Expert review of neurotherapeutics
  • 2008
Ex vivo endogenous tetrahydroisoquinolines may be transformed to neurotoxic N-methylated tetrahYDroisoquolines, both of which are known to induce PD-like motor symptoms.

Tolcapone decreases plasma levels of S-adenosyl-L-homocysteine and homocysteine in treated Parkinson’s disease patients

It is shown that COMT inhibition with tolcapone lowers tHcy synthesis and may hypothetically reduce homocysteine mediated progress of neuronal degeneration and the risk for onset of dementia, vascular disease and polyneuropathy in levodopa treated PD patients in the long term.

Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations.

Patients with PD and hyperhomocysteinemia are more likely to be depressed and to perform worse on neuropsychometric tasks compared with normohomocysteinemic patients, and further research is warranted to see if hyperhomocytesteinemia is a reversible risk factor for neuropsychiatric burden in patients with PD.

Pharmacokinetic behaviour of levodopa and 3-O-methyldopa after repeat administration of levodopa/carbidopa with and without entacapone in patients with Parkinson’s disease

A possibly augmented LD absorption and a prolonged LD metabolism after EN supplementation may contribute to a more continuous LD delivery to the brain.

Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease.

This is the first report that levodopa-related hyperhomocysteinemia is associated with increased risk for coronary artery disease (CAD), and the findings have implications for the treatment of PD in patients at risk for vascular disease, and potentially for those at risk of dementia and depression.

Levodopa and 3-O-methyldopa in cerebrospinal fluid after levodopa-carbidopa association.

The subjects treated with Sinemet-CR had lower LD cerebrospinal fluid concentrations along with lower LD and higher 3-OMD plasma concentrations, which may be explained by means of a transport competition between LD and 3-O-methyldopa at blood brain barrier level.

Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease

Continuous intraduodenal infusion of the levodopa/carbidopa enteral gel as monotherapy is safe and clinically superior to a number of individually optimized combinations of conventional oral and subcutaneous medications in patients with motor fluctuations.