Subcutaneous Apomorphine in Parkinsonian on-Off Oscillations

Stibe, C.M.H.; Kempster, Peter; Lees, Andrew J.; Stern, Gerald

doi:10.1016/s0140-6736(88)91193-2

Cited by 294 publications

(145 citation statements)

References 8 publications

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“…When administered parenterally, apomorphine provides rapid benefit that lasts around 45 to 60 minutes 379,380 and can be useful for the acute management of unpredictable or levodopaunresponsive "off " episodes. Apomorphine is a lipophilic water-soluble compound that requires no active transport mechanism to reach the brain.…”

Section: Time (Months)mentioning

confidence: 99%

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Olanow¹,

Stern²,

Sethi³

2009

Neurology

760

658

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Parkinson disease (PD) is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. With the aging of the population, the frequency of PD is expected to increase dramatically in the coming decades. Current therapy is largely based on a dopamine replacement strategy, primarily using the dopamine precursor levodopa. However, chronic treatment is associated with the development of motor complications, and the disease is inexorably progressive. Further, advancing disease is associated with the emergence of features such as freezing, falling, and dementia which are not adequately controlled with dopaminergic therapies. Indeed, it is now appreciated that these nondopaminergic features are common and the major source of disability for patients with advanced disease. Many different therapeutic agents and treatment strategies have been evaluated over the past several years to try and address these unmet medical needs, and many promising approaches are currently being tested in the laboratory and in the clinic. As a result, there are now many new therapies and strategic approaches available for the treatment of the different stages of PD, with which the treating physician must be familiar in order to provide patients with optimal care. This monograph provides an overview of the management of PD patients, with an emphasis on pathophysiology, and the results of recent clinical trials. It is intended to provide physicians with an understanding of the different treatment options that are available for managing the different stages of the disease and the scientific rationale of the different approaches. 1 PD is the second most common neurodegenerative disorder, with an average age at onset of about 60 years. An estimated 5 million people throughout the world have PD, with 1 million individuals each in the United States and in Europe with the disorder. PD affects approximately 0.3% of the population and 1% to 2% of those older than 60 years.2 With the aging of the population and the substantial increase in the number of at-risk individuals older than 60 years, it is anticipated that the prevalence of PD will increase dramatically in the coming decades.

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Section: Time (Months)mentioning

confidence: 99%

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Olanow¹,

Stern²,

Sethi³

2009

Neurology

760

658

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“…Subsequently, as a result of new pump technology in the field of diabetes and the availability of the anti-emetic domperidone, a clinical trial of apomorphine infusion for the management of Parkinsonian ON-OFF oscillations was undertaken by Stibe and colleagues. 4 Published in 1988, this pivotal trial confirmed that apomorphine was the only clinically available DA that was equipotent to levodopa and it was subsequently licensed for the treatment of PD in the UK. Since that time, a range of randomised, controlled clinical trials (using apomorphine injection) and open, uncontrolled studies (using apomorphine infusion) have confirmed it as a highly effective therapy to help manage refractory motor fluctuations, with thousands of PD patients throughout the world benefitting from its use.…”

Section: Andrew Leesmentioning

confidence: 92%

Twenty Years of Apomorphine Therapy – How Does it Compare with Levodopa?

Lees¹,

Isaacson²

2015

European Neurological Review

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Apomorphine administered subcutaneously has provided clinicians with an effective option for the rapid resolution of the symptoms of Parkinson's disease (PD) for over a quarter of a century. It is available for use either as an intermittent injection or a continuous infusion, depending on the severity of the patient's symptoms. This satellite symposium, held during the 18th International Congress of Parkinson's Disease and Movement Disorders in Stockholm, Sweden, from 8-12 June 2014, and chaired by Professor Andrew Lees, set out to review the extensive clinical experience of subcutaneous apomorphine in the management of PD accumulated over the past 25 years. It also aimed to explore why it continues to play such a valuable therapeutic role in this setting. The presenters highlighted key clinical data demonstrating why apomorphine is an effective choice for the management of both motor and non-motor symptoms in PD. Results from the limited number of comparative studies of apomorphine continuous infusion with other therapies for complex PD suggest that it has a robust motor effect, resulting in a reduction of OFF periods comparable to that achieved with more invasive options such as intrajejunal levodopa infusion or deep brain stimulation. In a large European study, apomorphine infusion has been shown to provide similar improvements in health-related quality of life to intrajejunal levodopa infusion but with a superior side-effect profile. In addition, apomorphine infusion has demonstrated beneficial non-motor effects in PD patients and reports suggest it is associated with low rates of impulse control disorders (ICDs). The motor fluctuations that occur over time in PD patients treated with oral levodopa present a management challenge as the disease progresses. Many PD patients experience these OFF periods despite optimised oral therapy and the use of multiple medications. They are due to both end-of-dose wearing OFF and delayed time to ON (TTO). A prolonged TTO is common in PD patients who have gastroparesis (delayed gastric emptying) whereby the levodopa dose is delayed exiting the stomach and is slow in reaching its site of absorption in the small intestine. Alternative non-oral formulations that avoid the gastrointestinal route, such as subcutaneous apomorphine intermittent injection, have therefore been investigated for the relief of motor fluctuations in this setting. Interim results from the ongoing Apokyn for Motor IMProvement of Morning AKinesia Trial (AM IMPAKT) study have shown that subcutaneous apomorphine injection is a valuable treatment option in PD patients with morning akinesia. This is due to a delayed onset of levodopa dose as it produces a rapid and reliable TTO, with 95 % of patients achieving at least a 20-minute reduction in TTO and an average reduction of 40 minutes. Patients also experienced improvements in Unified Parkinson's Disease Rating Scale (UPDRS) motor score and Hoehn and Yahr stage, as well as measures of quality of life and global impression of severity.

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“…This drug is largely an anti-histamine with low affinities for dopamine receptors thus producing antiemetic effects without antidopaminergic properties [26]. The majority of the therapeutic trials conducted in the late 1980s and 1990s consistently demonstrated a reduction in the number of daily 'off' periods [4,25,[27][28][29][30][31]. These trials also showed the majority of patients had a reduction in other 'off' phenomenon such as early morning dystonia, dysphagia, anismus, urinary dysfunction and 'off' period pain [4,27,28,[31][32][33].…”

Section: Early Clinical Data In Pdmentioning

confidence: 99%

Role of Apomorphine in the Treatment of Parkinson’s Disease

Boyle

Ondo

2015

CNS Drugs

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Current research shows that apomorphine is an effective treatment for symptoms of Parkinson's Disease (PD). The highly lipophilic structure allows apomorphine to cross cell membranes rapidly, leading to the rapid onset of action for on/off symptoms of PD. The use of apomorphine was limited in the past due to peripheral side effects, but with the advent of better delivery systems and medications to control side effects, apomorphine is better tolerated and more widely in use. The major delivery systems are continuous subcutaneous infusions and intermittent subcutaneous injections, but other delivery routes are under investigation. The purpose of this article is to discuss the current use of apomorphine, the current delivery systems and to discuss future research. Key PointsApomorphine is an effective symptomatic treatment for PD.The highly lipophilic nature allows for rapid transit to the CNS.Rapid onset of action allows for fast abortion of PD 'off' time symptoms.Most common delivery methods are continuous or intermittent subcutaneous infusion/injection.

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Subcutaneous Apomorphine in Parkinsonian on-Off Oscillations

Cited by 294 publications

References 8 publications

The scientific and clinical basis for the treatment of Parkinson disease (2009)

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Twenty Years of Apomorphine Therapy – How Does it Compare with Levodopa?

Role of Apomorphine in the Treatment of Parkinson’s Disease

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