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Journal of Neural Transmission (Vienna,... Nov 2023Subcutaneous apomorphine infusion is a device-aided therapy for Parkinson's disease that can be considered when motor fluctuations become persistent and are no longer... (Randomized Controlled Trial)
Randomized Controlled Trial
Subcutaneous apomorphine infusion is a device-aided therapy for Parkinson's disease that can be considered when motor fluctuations become persistent and are no longer adequately controlled by oral/transdermal medication. Apomorphine infusion is less invasive than enteral levodopa, deep brain stimulation or focused ultrasound, and is often indicated even when neurosurgical approaches are contraindicated. This article aims to provide practical guidance for doctors and nurses initiating and treating patients with apomorphine infusion, and is based on both trial data and clinical experience from movement disorders specialists. A post hoc analysis of data from the TOLEDO randomized clinical trial of apomorphine infusion was conducted along with an analysis of 'real world' experience from 13 movement disorders specialists using a questionnaire that focused on starting patients on apomorphine infusion. Practical guidelines for starting treatment with apomorphine infusion are provided taking into consideration the regional disparities in healthcare. Apomorphine infusion is straightforward to administer but to be successful it requires concordance from the patient and family, and clinical support from an experienced team of doctors and nurses, particularly in the early months of treatment.
Topics: Humans; Apomorphine; Parkinson Disease; Antiparkinson Agents; Levodopa; Infusions, Parenteral
PubMed: 37658155
DOI: 10.1007/s00702-023-02686-7 -
Clinical and Translational Science Jul 2021Apomorphine is an on-demand treatment of "OFF" episodes in patients with Parkinson's disease (PD). A joint parent-metabolite population pharmacokinetic (PK) model...
Apomorphine is an on-demand treatment of "OFF" episodes in patients with Parkinson's disease (PD). A joint parent-metabolite population pharmacokinetic (PK) model characterized apomorphine and apomorphine-sulfate following administration of apomorphine sublingual film (APL) and two formulations of subcutaneous apomorphine. Overall, 2485 samples from 87 healthy subjects and 71 patients with PD and "OFF" episodes were analyzed using nonlinear mixed-effects modeling. Apomorphine PK was adequately described by a two-compartment model with first-order transit absorption via both routes of administration and first-order metabolism to apomorphine-sulfate with one-compartment disposition and first-order elimination. Bioavailability of apomorphine sublingual film was ~ 18% relative to subcutaneous apomorphine. Among covariates tested, only body weight had a large effect on apomorphine exposure (maximum plasma concentration and area under the concentration-time curve [AUC ]), with greater weight resulting in lower exposure. Model-predicted apomorphine exposure was similar between apomorphine sublingual film 30 mg and subcutaneous apomorphine 5 mg (median AUC , 66.7 ng•h/mL, geometric mean ratio of 0.99; 90% confidence interval [CI], 0.96-1.03) and was comparable between apomorphine sublingual film 35 mg and subcutaneous apomorphine 6 mg (median AUC , 75.4 and 80.0 ng•h/mL, respectively; geometric mean ratio of 0.94; 90% CI, 0.90-0.97) administered every 2 h for a maximum of 5 doses per day. In a typical patient with PD, predicted apomorphine exposure increased with increasing doses of apomorphine sublingual film; however, the increase was less than dose proportional. Similar apomorphine exposure was predicted in patients with mild renal impairment versus normal renal function. PK properties of apomorphine sublingual film support its administration for a wide range of patients with PD and "OFF" episodes, regardless of demographic and clinical characteristics.
Topics: Administration, Sublingual; Adult; Aged; Aged, 80 and over; Antiparkinson Agents; Apomorphine; Area Under Curve; Biological Availability; Biological Variation, Population; Clinical Trials as Topic; Female; Healthy Volunteers; Humans; Injections, Subcutaneous; Male; Middle Aged; Models, Biological; Oral Mucosal Absorption; Parkinson Disease; Young Adult
PubMed: 33650272
DOI: 10.1111/cts.13008 -
Annals of Neurology Feb 2011
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Apomorphine; Autophagy; Dopamine Agonists; Mice; Oxidative Stress
PubMed: 21387363
DOI: 10.1002/ana.22359 -
Molecules (Basel, Switzerland) May 2012Apomorphine (APO) is an aporphine derivative used in human and veterinary medicine. APO activates D₁, D(2S), D(2L), D₃, D₄, and D₅ receptors (and is thus... (Review)
Review
Apomorphine (APO) is an aporphine derivative used in human and veterinary medicine. APO activates D₁, D(2S), D(2L), D₃, D₄, and D₅ receptors (and is thus classified as a non-selective dopamine agonist), serotonin receptors (5HT(1A), 5HT(2A), 5HT(2B), and 5HT(2C)), and α-adrenergic receptors (α(1B), α(1D), α(2A), α(2B), and α(2C)). In veterinary medicine, APO is used to induce vomiting in dogs, an important early treatment for some common orally ingested poisons (e.g., anti-freeze or insecticides). In human medicine, it has been used in a variety of treatments ranging from the treatment of addiction (i.e., to heroin, alcohol or cigarettes), for treatment of erectile dysfunction in males and hypoactive sexual desire disorder in females to the treatment of patients with Parkinson's disease (PD). Currently, APO is used in patients with advanced PD, for the treatment of persistent and disabling motor fluctuations which do not respond to levodopa or other dopamine agonists, either on its own or in combination with deep brain stimulation. Recently, a new and potentially important therapeutic role for APO in the treatment of Alzheimer's disease has been suggested; APO seems to stimulate Aβ catabolism in an animal model and cell culture, thus reducing the rate of Aβ oligomerisation and consequent neural cell death.
Topics: Alzheimer Disease; Animals; Apomorphine; Dogs; Dopamine Agonists; Erectile Dysfunction; Female; Humans; Male; Parkinson Disease; Receptors, Adrenergic, alpha; Receptors, Dopamine; Receptors, Serotonin; Substance-Related Disorders
PubMed: 22565480
DOI: 10.3390/molecules17055289 -
Revista de Neurologia May 2021Apomorphine, a D1-D2 dopamine agonist, is the oldest drug with proven efficacy in the treatment of Parkinson's disease (PD), and the only with similar symptomatic power... (Review)
Review
INTRODUCTION
Apomorphine, a D1-D2 dopamine agonist, is the oldest drug with proven efficacy in the treatment of Parkinson's disease (PD), and the only with similar symptomatic power to levodopa. Its usefulness in the control of motor fluctuations, both as intermittent injections and in continuous subcutaneous infusion, has been demonstrated in open label and placebo controlled trials.
AIM
To analyse the role of apomorphine in the varied clinical symptoms and different clinical stages of PD through a narrative review of scientific literature (1951-2020).
DEVELOPMENT
Beyond on-time increase, off-time decrease, off dystonia and quality of life improvement in advanced PD, there is evidence to support a role of apomorphine in less known clinical areas of PD, such as non motor symptoms, a lower risk of impulse control disorders, potential to ameliorate visual hallucinations, improve neuropsychiatric symptoms and dyskinesia and even axial features. Nevertheless, the optimal timing of apomorphine treatment remains controversial, and its implementation of this valuable drug in clinical practice has been historically hindered by several factors.
CONCLUSIONS
Apomorphine is a unique drug in the PD treatment scenario, with a number of potential applications beyond motor fluctuations control. Acknowledging these properties, selecting the patient most likely to benefit from it and finding the right timing may be key in the symptomatic control of this complex disease.
Topics: Apomorphine; Dopamine Agonists; Humans; Parkinson Disease
PubMed: 33908619
DOI: 10.33588/rn.7209.2020658 -
Neurologia (Barcelona, Spain) 2013Many patients who have had Parkinson's disease (PD) for several years will present severe motor fluctuations and dyskinesias which require more aggressive therapies. The... (Review)
Review
INTRODUCTION
Many patients who have had Parkinson's disease (PD) for several years will present severe motor fluctuations and dyskinesias which require more aggressive therapies. The different approaches which are now available include deep brain stimulation of the subthalamic nucleus or medial globus pallidus, subcutaneous infusion of apomorphine, and intestinal infusion of levodopa-carbidopa.
OBJECTIVE
To define the indications and results for the 3 available therapies for advanced PD.
DEVELOPMENT
Exhaustive review of the literature concerning the indications and results of deep brain stimulation, subcutaneous apomorphine infusion and duodenal infusion of levodopa/carbidopa gel to treat patients with advanced Parkinson disease.
CONCLUSIONS
Although numerous studies have confirmed the efficacy of the 3 different therapies in advanced PD, there are no comparative studies that would allow us to define the best candidate for each technique.
Topics: Antiparkinson Agents; Apomorphine; Cognition Disorders; Deep Brain Stimulation; Disease Progression; Humans; Infusions, Intravenous; Parkinson Disease; Psychotic Disorders
PubMed: 23880230
DOI: 10.1016/j.nrl.2013.05.002 -
CNS Drugs Dec 2022Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced... (Meta-Analysis)
Meta-Analysis
Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis.
INTRODUCTION
Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson's disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD.
METHODS
A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson's Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson's Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness.
RESULTS
A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5-70.9 years, duration of PD was 9.1-15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL.
CONCLUSIONS
This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.
Topics: Humans; Middle Aged; Aged; Carbidopa; Levodopa; Quality of Life; Network Meta-Analysis; Parkinson Disease; Apomorphine
PubMed: 36414908
DOI: 10.1007/s40263-022-00963-9 -
Anaesthesia 1978
Topics: Anesthesia, Obstetrical; Apomorphine; Cesarean Section; Female; Humans; Pregnancy; Vomiting
PubMed: 686344
DOI: 10.1111/j.1365-2044.1978.tb08450.x -
Brain and Behavior May 2022Parkinson's disease is one of the progressive neurodegenerative diseases from which people suffer for years. The mechanism of this disease is associated with a decrease...
INTRODUCTION
Parkinson's disease is one of the progressive neurodegenerative diseases from which people suffer for years. The mechanism of this disease is associated with a decrease in the number of dopaminergic neurons in the substantia nigra (SN) while Lewy bodies are still present. As a result, both motor-ridity, tremor, and bradykinesia-and non-motor symptoms such as anxiety and depression. Nowadays, it is well known that the cause behind Parkinson's disease is mainly environmental changes, genetic susceptibility, and toxins. Unfortunately, there is no cure for the disease but treatments. The replacement of lost neurons, α-synuclein and apomorphine, is currently being studied for new therapies. This article focuses on history, mechanism, factors causing Parkinson's disease as well as future therapies for the cure of the diseases.
METHODOLOGY
Data were collected from medical journals published on PubMed, The Lancet, Cells, and Nature Reviews Neurology databases with a predefined search strategy. All articles considering new therapies for Parkinson's disease were considered.
RESULTS
The pathophysiology of Parkinson's disease is currently reasonably understood. However, there is no definitive cure so all the treatments focus mainly on reducing or limiting the symptoms. Current treatment studies focus on genetics, replacing lost neurons, α-synuclein and apomorphine.
CONCLUSION
Parkinson's disease is the most common movement disorder worldwide because of the loss of dopaminergic neurons in the substantia nigra. Its symptoms include motor dysfunctions such as rigidity, tremor, and bradykinesia and non-motor dysfunctions such as anxiety and depression. Through genetics, environmental changes and toxins analysis, it is now known that future new therapies are working on replacing lost neurons, α-synuclein and apomorphine.
Topics: Apomorphine; Dopaminergic Neurons; Humans; Hypokinesia; Parkinson Disease; Tremor; alpha-Synuclein
PubMed: 35451243
DOI: 10.1002/brb3.2577 -
Tremor and Other Hyperkinetic Movements... 2021Apomorphine is a potent dopamine agonist used in the treatment of advanced and fluctuating Parkinson's Disease. However the need for its subcutaneous infusion can lead...
BACKGROUND
Apomorphine is a potent dopamine agonist used in the treatment of advanced and fluctuating Parkinson's Disease. However the need for its subcutaneous infusion can lead to skin reactions.
PHENOMENOLOGY SHOWN
We illustrate necrotic ulcers at infusion sites as a rare event during continuous subcutaneous apomorphine infusion.
EDUCATIONAL VALUE
This case demonstrates the rare adverse event of necrotic ulcers in a patient with long term apomorphine infusion.
Topics: Antiparkinson Agents; Apomorphine; Dopamine Agonists; Humans; Injections, Subcutaneous; Ulcer
PubMed: 35070491
DOI: 10.5334/tohm.648