Continuous intestinal infusion of levodopa/carbidopa in advanced Parkinson's disease: ef fi cacy, safety and patient selection.
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Long-term oral therapy with levodopa is associated with the development of motor fl uctuations and dyskinesia in a large percentage of patients with Parkinson's disease (PD). Motor complications are associated with a number of non-motor symptoms and have a negative impact on disability and quality of life. There are three therapeutic options available for the management of patients at this advanced stage: high frequency deep brain stimulation, continuous subcutaneous infusion of apomorphine, and continuous intestinal infusion of levodopa/carbidopa. On the basis of published data and in consideration of the risk-bene fi t pro fi le of current therapeutic strategies, we here propose an algorithm to help clinicians select the most suitable treatment option for patients with advanced PD. (+info)
Motor matters: tackling heterogeneity of Parkinson's disease in functional MRI studies.
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Population pharmacodynamics of IPX066: an oral extended-release capsule formulation of carbidopa-levodopa, and immediate-release carbidopa-levodopa in patients with advanced Parkinson's disease.
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A rapid non invasive L-DOPA-(1)(3)C breath test for optimally suppressing extracerebral AADC enzyme activity - toward individualizing carbidopa therapy in Parkinson's disease.
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BACKGROUND: Peripheral carbidopa (CD) levels directly impact on central dopamine (DA) production in Parkinson disease (PD) through extracerebral inhibition of dopa decarboxylase (AADC) resulting in an increase in levodopa (LD) bioavailability. OBJECTIVE: Recent data suggests that higher CD doses than those presently used in PD treatment may result in improved clinical response. Optimizing CD doses in individual patients may, therefore, result in ideal individualized treatment. METHODS: A single center, randomized, double-blind study was carried out recruiting 5 Parkinson's disease (PD) patients already on LD/CD and 1 treatment nave PD patient using stable isotope labeled LD-1-(1)(3)C as a substrate for a noninvasive breath test to evaluate individual AADC enzyme activity. Each patient was studied five times, receiving 200 mg LD-(1)(3)C at each visit along with one of five randomized CD doses (0, 25, 50, 100 and 200 mg). The metabolite (1)(3)CO(2) in breath was measured for evaluating AADC enzyme activity and plasma metabolite levels for LD-(1)(3)C and homovanillic acid (HVA) were measured for 4 hours. RESULTS: HVA in plasma and (1)(3)CO(2) in breath are metabolic products of LD. We found a significant positive correlation of (1)(3)CO(2) DOB AUC0-240 with serum HVA AUC0-240 following the oral dose of LD-1-(1)(3)C for all 5 doses of CD (r(2) = 0.9378). With increasing inhibition of AADC enzyme activity with CD, we observed an increase in the plasma concentration of LD.We found an inverse correlation of the 13CO2 DOB AUC with serum LD-(1)(3)C AUC. Our studies indicate the optimal dose of CD for maximal suppression of AADC enzyme activity can be determined for each individual from (1)(3)CO(2) generation in breath. CONCLUSIONS: The LD-breath test can be a useful noninvasive diagnostic tool for evaluation of AADC enzyme activity using the biomarker (1)(3)CO(2) in breath, a first step in personalizing CD doses for PD patients. (+info)
Neuropathy in Parkinson's disease patients with intestinal levodopa infusion versus oral drugs.
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