Levodopa availability improves with progression of Parkinson’s disease

Woitalla, Dirk; Goetze, Oliver; Kim, Jeong I.; Nikodem, Alice; Schmidt, Wolfgang E.; Przuntek, H.; Müller, Thomas

doi:10.1007/s00415-006-0207-y

Cited by 18 publications

(13 citation statements)

References 28 publications

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“…Motor complications, such as dyskinesias, that become manifest in advanced stages of the disease after chronic levodopa treatment, could be related to inhomogeneous drug delivery as a result of barrier compromise, or to a reduced capacity of the Na + dependent transport system to remove levodopa from the brain extracellular fluid. The latter hypothesis well fits with a previous study on high levodopa availability in advanced PD patients [19]. …”

Section: Discussionsupporting

confidence: 92%

Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease

Pisani

Stefani

Pierantozzi

et al. 2012

J Neuroinflammation

126

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BackgroundAlterations in blood–brain barrier permeability have been proposed to represent a relevant factor contributing to Parkinson’s disease progression. However, few studies have addressed this issue in patients at different stages of disease.MethodsAlbumin was measured in cerebrospinal fluid and serum samples obtained from 73 non-demented subjects with idiopathic Parkinson’s disease and 47 age-matched control subjects. The albumin ratio (AR) was calculated to assess blood-cerebrospinal fluid and blood–brain barrier function. The group of patients with Parkinson’s disease included 46 subjects with Hoehn-Yahr staging between 1 and 2 and 27, with a score ranging from 2.5 to 4.ResultsStatistically significant differences in albumin ratio were found between patients with advanced disease, and both early-stage and unaffected groups. Conversely, early-phase patients did not differ from healthy subjects. Additionally, dopaminergic treatment seems to exert a possible effect on AR values.ConclusionsOur study demonstrates that possible dysfunction of the blood-cerebrospinal fluid barrier, blood–brain barrier, or both, characterize Parkinson’s disease progression. The associations between clinical scores, treatments and biochemical findings suggest a progressive impairment of barrier integrity during the course of the disease.

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Section: Discussionsupporting

confidence: 92%

Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease

Pisani

Stefani

Pierantozzi

et al. 2012

J Neuroinflammation

126

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“…In this context it is of note that in Parkinson's disease patients factors are described influencing the pharmacokinetics of levodopa, e.g. increasing enteric dysfunction with disease severity or altered peripheral dopa-decarboxylase activity [19,20]. While these factors might influence a possible interaction they lead, however, to an increased variability and the detection of an interaction therefore may be difficult.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the impact of sarizotan on the pharmacokinetics of levodopa

Krösser

Neugebauer

Chassard³

et al. 2007

Biopharm & Drug Disp

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“…Generally, LD uptake depends on the gastric emptying time, gastrointestinal absorption and transport via the gastrointestinal amino acid transporter system. 28,[68][69][70][71][72] PD Patients often receive a drug combination therapy that involves multiple daily dosing of a particular compound and additional supplementation with other drugs at least partially sharing the modes of action. Efficacy of all administered compounds depends on patient compliance, the nature of the delivery system, physicochemical properties of the drug and physiological considerations.…”

Section: Gastrointestinal Absorptionmentioning

confidence: 99%

The Impact of COMT-inhibition on Gastrointestinal Levodopa Absorption in Patients with Parkinson's Disease

Müller

2010

Clinical Medicine Insights: Therapeutics

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The drug Levodopa (LD) is an efficient compound for the treatment of patients with Parkinson's disease (PD). Its short half life generates plasma behaviour of LD with peaks and troughs. Therefore, following the LD transport into the brain and the conversion to dopamine, an alternating stimulation of nigrostriatal postsynaptic dopamine receptors takes place. In the long term these fluctuations of dopamine concentrations supports onset of motor complications (MC) in PD patients. General opinion is that loss of central compensatory mechanisms of dopamine metabolism is responsible for the development of MC. However, in the periphery, LD troughs are preponderantly associated with the MC wearing off, which is the reappearance of motor symptoms with decreasing drug effect. Addition of the catechol-O-methyltransferase (COMT) inhibitor Entacapone (EN) to LD/carbidopa (CD) improved wearing off, since EN prolongs LD half life and avoids troughs. Plasma LD peaks are mostly related to the clinical manifestation of the MC dyskinesia, which appear as involuntary movements. One time addition of EN to a LD/CD formulation showed no increase of peripheral maximum LD concentration. But repeat combination of EN to each LD/CD intake elevated plasma LD bioavailability and peaks. Therefore switch from a LD/CD-to a LD/CD/EN regime may also ask for reduction of LD/CD dosing or delay of the next LD/CD intake, to avoid onset of the most common peak dose dyskinesia. In conclusion, pharmacokinetic studies on peripheral LD metabolism and mode of intake underline their importance as peripheral components for MC manifestations in PD patients.

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Levodopa availability improves with progression of Parkinson’s disease

Abstract: Levodopa availability improves with progression of PD. This may result from deteriorated peripheral activity of levodopa metabolising enzymes or an increasing enteric dysfunction with subsequent better duodenal levodopa absorption or both.

Cited by 18 publications

References 28 publications

Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease

Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease

Investigation of the impact of sarizotan on the pharmacokinetics of levodopa

The Impact of COMT-inhibition on Gastrointestinal Levodopa Absorption in Patients with Parkinson's Disease

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