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European Neurology 2017To assess the efficacy and safety of adjuvant treatment with entacapone in the treatment of later Parkinson's disease (PD) patients with motor fluctuation. (Meta-Analysis)
Meta-Analysis Review
AIMS
To assess the efficacy and safety of adjuvant treatment with entacapone in the treatment of later Parkinson's disease (PD) patients with motor fluctuation.
METHODS
We conducted a systematic review of relevant studies from 8 databases to June 23, 2016.
RESULTS
Fourteen studies were included in this review (n = 2,804). The results showed that compared with placebo, adjuvant therapy with entacapone significantly increased on time (p < 0.01) and reduced off time (p < 0.01), the required levodopa (LD) dose (p < 0.01) and improved Parkinson's Disease Rating Scale (UPDRS) scores (activities of daily living score: p < 0.01; motor score: p < 0.01; UPDRS I-III score: p > 0.05). However, the withdrawal (OR 1.44, 95% CI 1.10-1.89, p < 0.01) due to adverse events and adverse events rates including nausea (OR 2.23, 95% CI 1.56-3.20, p < 0.01), urine discoloration (OR 14.99, 95% CI 7.63-29.44, p < 0.01), gastrointestinal disorder (OR 2.6, 95% CI 1.89-3.57, p < 0.01) and dyskinesia (OR 2.00, 95% CI 1.56-2.58, p < 0.01) increased in patients with entacapone compared with those given a placebo .
CONCLUSIONS
This meta-analysis suggests that the entacapone used as adjuvant therapy to LD is effective in the management of later PD with fluctuation. However, patients on entacapone had a higher frequency of adverse events than those on placebo but no occurrence of severe adverse reactions.
Topics: Activities of Daily Living; Aged; Antiparkinson Agents; Catechols; Drug Therapy, Combination; Dyskinesias; Female; Humans; Levodopa; Male; Middle Aged; Nitriles; Parkinson Disease
PubMed: 28813703
DOI: 10.1159/000479555 -
Clinical Pharmacokinetics Sep 2017Parkinson's disease (PD) is a chronic progressive neurological disorder characterized by resting tremor, rigidity, bradykinesia, gait disturbance, and postural... (Review)
Review
Parkinson's disease (PD) is a chronic progressive neurological disorder characterized by resting tremor, rigidity, bradykinesia, gait disturbance, and postural instability. Levodopa, the precursor to dopamine, coadministered with carbidopa or benserazide, aromatic amino acid decarboxylase inhibitors, is the most effective and widely used therapeutic agent in the treatment of PD. With continued levodopa treatment, a majority of patients develop motor complications such as dyskinesia and motor 'on-off' fluctuations, which are, in part, related to the fluctuations in plasma concentrations of levodopa. A new extended-release (ER) carbidopa-levodopa capsule product (also referred to as IPX066) was developed and approved in the US as Rytary and in the EU as Numient. The capsule formulation is designed to provide an initial rapid absorption of levodopa comparable to immediate-release (IR) carbidopa-levodopa, and to subsequently provide stable levodopa concentrations with reduced peak-to-trough excursions in plasma concentrations in order to reduce motor fluctuations associated with pulsatile stimulation of dopamine receptors and to minimize dyskinesia. Phase III studies of this ER carbidopa-levodopa capsule formulation in patients with PD have shown a significant reduction in 'off' time compared with IR carbidopa-levodopa and carbidopa-levodopa-entacapone. We present a review of the clinical pharmacokinetics and pharmacodynamics of this ER product of carbidopa-levodopa in healthy subjects and in patients with PD.
Topics: Animals; Antiparkinson Agents; Capsules; Carbidopa; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Combinations; Drug Compounding; Humans; Levodopa; Parkinson Disease
PubMed: 28236251
DOI: 10.1007/s40262-017-0511-y -
Journal of Parkinson's Disease 2020Parkinson's disease (PD) is a condition that predominantly affects older people. It is imperative that clinical management considers the other significant illnesses that... (Review)
Review
Parkinson's disease (PD) is a condition that predominantly affects older people. It is imperative that clinical management considers the other significant illnesses that people with PD accumulate as they age in conjunction with their resilience to cope with physiological change. Multimorbidity and frailty act synergistically to heighten the risk of adverse outcomes for older people with PD. These states are associated with increased likelihood of hospitalization, polypharmacy, adverse drug effects including the anticholinergic burden of medications, drug-disease and drug-drug interactions. Management should be integrated, holistic and individualised to meticulously balance the risks of interventions considering the vulnerability of the individual to recover from disturbance to their environmental, physical and cognitive equilibrium.
Topics: Aged; Antiparkinson Agents; Drug-Related Side Effects and Adverse Reactions; Frail Elderly; Frailty; Hospitalization; Humans; Multimorbidity; Parkinson Disease; Polypharmacy
PubMed: 32741841
DOI: 10.3233/JPD-202105 -
Journal of Neural Transmission (Vienna,... Nov 2023Device-aided therapies (DAT), which include deep brain stimulation and pump-based continuous dopaminergic stimulation with either levodopa or apomorphine, are among the... (Review)
Review
Device-aided therapies (DAT), which include deep brain stimulation and pump-based continuous dopaminergic stimulation with either levodopa or apomorphine, are among the major advances in the clinical management of Parkinson's disease (PD). Although DAT are being increasingly offered earlier in the disease course, their classical indication remains advanced PD. Theoretically, every patient should be offered transition to DAT when faced with refractory motor and nonmotor fluctuations and functional decline. Worldwide clinical reality is far from these ideal, and, therefore, question the "real-world" equal opportunity of access to DAT for PD patients with advanced PD-even within a single health care system. Differences in access to care, referral pattern (timing and frequency), as well as physician biases (unconscious/implicit or conscious/explicit bias), and patients' preferences or health-seeking behaviour are to be considered. Compared to DBS, little information is available concerning infusion therapies, as well as neurologists' and patients' attitudes towards them. This viewpoint aims to be thought-provoking and to assist clinicians in moving through the process of DAT selection, by including in their decision algorithm their own biases, patient perspective, ethical concerns as well as the current unknowns surrounding PD prognosis and DAT-related long-term side effects for a given patient.
Topics: Humans; Parkinson Disease; Antiparkinson Agents; Prognosis; Patient Preference; Uncertainty; Levodopa; Deep Brain Stimulation
PubMed: 37436446
DOI: 10.1007/s00702-023-02668-9 -
Arquivos de Neuro-psiquiatria Dec 2018Optimizing idiopathic Parkinson's disease treatment is a challenging, multifaceted and continuous process with direct impact on patients' quality of life. The basic... (Review)
Review
Optimizing idiopathic Parkinson's disease treatment is a challenging, multifaceted and continuous process with direct impact on patients' quality of life. The basic tenet of this task entails tailored therapy, allowing for optimal motor function with the fewest adverse effects. Apomorphine, a dopamine agonist used as rescue therapy for patients with motor fluctuations, with potential positive effects on nonmotor symptoms, is the only antiparkinsonian agent whose capacity to control motor symptoms is comparable to that of levodopa. Subcutaneous administration, either as an intermittent injection or as continuous infusion, appears to be the most effective and tolerable route. This review summarizes the historical background, structure, mechanism of action, indications, contraindications and side effects, compares apomorphine infusion therapy with other treatments, such as oral therapy, deep brain stimulation and continuous enteral infusion of levodopa/carbidopa gel, and gives practical instructions on how to initiate treatment.
Topics: Antiparkinson Agents; Apomorphine; Carbidopa; Deep Brain Stimulation; Dopamine Agonists; Drug Combinations; Humans; Levodopa; Parkinson Disease
PubMed: 30698208
DOI: 10.1590/0004-282X20180140 -
Current Neuropharmacology 2023Parkinson's disease (PD) is one of the most common neurodegenerative diseases, characterized by the reduction of dopamine neurons in the substantia nigra. Levodopa, as a... (Review)
Review
Parkinson's disease (PD) is one of the most common neurodegenerative diseases, characterized by the reduction of dopamine neurons in the substantia nigra. Levodopa, as a dopamine supplement, is the gold-standard therapeutic drug for PD. The metabolism of levodopa in the periphery not only decreases its bioavailability but also affects its efficacy. Thus, it is necessary to investigate how levodopa is metabolized. A growing number of studies have shown that intestinal bacteria, such as Enterococcus faecalis, Eggerthella lenta and Clostridium sporogenes, could metabolize levodopa in different ways. In addition, several pathways to reduce levodopa metabolism by gut microbiota were confirmed to improve levodopa efficacy. These pathways include aromatic amino acid decarboxylase (AADC) inhibitors, antibiotics, pH and (S)-α-fluoromethyltyrosine (AFMT). In this review, we have summarized the metabolic process of levodopa by intestinal bacteria and analyzed potential approaches to reduce the metabolism of levodopa by gut microbiota, thus improving the efficacy of levodopa.
Topics: Humans; Levodopa; Antiparkinson Agents; Parkinson Disease; Dopamine; Bacteria
PubMed: 36278467
DOI: 10.2174/1570159X21666221019115716 -
Drug Design, Development and Therapy 2021Parkinson's therapeutic interventions are only symptomatic. An optimal treatment should therefore address the largest number of motor and non-motor symptoms, to manage... (Review)
Review
INTRODUCTION
Parkinson's therapeutic interventions are only symptomatic. An optimal treatment should therefore address the largest number of motor and non-motor symptoms, to manage patients at best. Safinamide is one of the most recent approved drugs for fluctuating patients, in add-on to levodopa, that remains the gold standard treatment. It has a unique mechanism of action, both dopaminergic (as MAO-B inhibitor) and glutamatergic (through Na channel blockade). Results from Phase III trials, post-hoc analyses and real-life experiences suggest a beneficial effect on motor (such as tremor, bradykinesia, rigidity and gait) and non-motor (pain, mood, sleep) symptoms.
AREAS COVERED
Here, the authors discuss clinical efficacy and safety of safinamide, identifying the patients' profiles that could benefit most. A search in PubMed was performed in September 2020, with no time limits. Publications' abstracts were reviewed.
CONCLUSION
Safinamide is peculiar due to its double mechanism of action. Its benefits in improving motor functions and fluctuations, and some non-motor symptoms, could have a valuable impact on patients' quality of life (QoL), together with its safety profile.
Topics: Alanine; Animals; Antiparkinson Agents; Benzylamines; Drug Therapy, Combination; Humans; Levodopa; Monoamine Oxidase Inhibitors; Parkinson Disease; Quality of Life; Treatment Outcome
PubMed: 34140766
DOI: 10.2147/DDDT.S302673 -
Parkinsonism & Related Disorders Apr 2022The objective of this study was to compare the pharmacokinetics (PK) of levodopa (LD) from 24-h continuous subcutaneous infusion of foslevodopa/foscarbidopa to the LD... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The objective of this study was to compare the pharmacokinetics (PK) of levodopa (LD) from 24-h continuous subcutaneous infusion of foslevodopa/foscarbidopa to the LD pharmacokinetics from 16-h levodopa-carbidopa intestinal gel (LCIG) followed by night-time oral LD/carbidopa (CD) doses.
METHODS
This was a Phase 1, open-label, randomized, 2-period crossover study conducted in 25 male and female healthy volunteers.
RESULTS
The LD exposures (C, AUC and AUC∞) following subcutaneous infusion of 700/35 mg foslevodopa/foscarbidopa over 24 h were similar (<8% difference) to those of LCIG 350/87.5 mg LD/CD administered over 16 h followed by two 100/25 mg LD/CD oral doses at 18 and 21 h after the start of LCIG delivery.
CONCLUSION
Foslevodopa/foscarbidopa subcutaneous infusion provides levodopa exposures comparable to LCIG throughout the day.
GOV IDENTIFIER
Not Applicable.
Topics: Antiparkinson Agents; Carbidopa; Cross-Over Studies; Dopamine Agonists; Drug Combinations; Female; Gels; Humans; Infusions, Subcutaneous; Jejunum; Levodopa; Male; Parkinson Disease
PubMed: 35339102
DOI: 10.1016/j.parkreldis.2022.03.012 -
Ideggyogyaszati Szemle May 2021Despite the continuous development of diagnosis and treatment of patients with Parkinson's disease and the arrival of new therapeutic options in recent years the... (Review)
Review
Despite the continuous development of diagnosis and treatment of patients with Parkinson's disease and the arrival of new therapeutic options in recent years the treatment and care of people with Parkinson's disease especially in the advanced stage remains a major challenge for neurologists specialized in movement disorders. The treatment of Parkinson's disease is adversely affected by several factors: the disease progresses relentlessly, the symptoms and rate of progression, other concomitant non-motor symptoms, and the appearance of complications caused by treatment show great heterogeneity. Based on all these factors it is difficult to develop and apply a uniform routine therapeutic guideline. This summary seeks to shed light on aspects of the treatment of Parkinson's disease particularly in advanced-stage cases drawing on data from a professional college recommendation and the literature.
Topics: Antiparkinson Agents; Humans; Levodopa; Parkinson Disease
PubMed: 34106553
DOI: 10.18071/isz.74.0151 -
Acta Pharmacologica Sinica Apr 2020Motor control in the striatum is an orchestra played by various neuronal populations. Loss of harmony due to dopamine deficiency is considered the primary pathological... (Review)
Review
Motor control in the striatum is an orchestra played by various neuronal populations. Loss of harmony due to dopamine deficiency is considered the primary pathological cause of the symptoms of Parkinson's disease (PD). Recent progress in experimental approaches has enabled us to examine the striatal circuitry in a much more comprehensive manner, not only reshaping our understanding of striatal functions in movement regulation but also leading to new opportunities for the development of therapeutic strategies for treating PD. In addition to dopaminergic innervation, giant aspiny cholinergic interneurons (ChIs) within the striatum have long been recognized as a critical node for balancing dopamine signaling and regulating movement. With the roles of ChIs in motor control further uncovered and more specific manipulations available, striatal ChIs and their corresponding receptors are emerging as new promising therapeutic targets for PD. This review summarizes recent progress in functional studies of striatal circuitry and discusses the translational implications of these new findings for the treatment of PD.
Topics: Animals; Antiparkinson Agents; Cholinergic Agents; Cholinergic Neurons; Humans; Parkinson Disease
PubMed: 32132659
DOI: 10.1038/s41401-020-0380-z