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Impact of motor fluctuations on quality of life

Parkinson’s disease is characterized by neurodegeneration of the substantia nigra resulting in dopamine deficiency, and associated motor and non-motor symptoms. Although dopamine replacement therapy is effective, most patients experience motor fluctuations as the disease progresses.12

The development of motor fluctuations and dyskinesia represent an important milestone in the progression of Parkinson’s disease and characterizes the transition from early to advanced PD.4 Over time, these fluctuations typically worsen and persist despite repeated adjustments of oral and transdermal medications.12

As the degeneration of the dopaminergic neurons progresses, peaks and troughs in plasma levodopa concentrations after dosing are increasingly mirrored in the striatal dopamine concentrations, and it is these large fluctuations that lead to motor complications. High striatal dopamine levels over-stimulate receptors, leading to worsening dyskinesia, and low levels lead to too little movement or ‘wearing off’.13

Progressive degeneration of dopaminergic neurons in advancing Parkinson’s disease

Early Parkinson’s disease

  • Surviving nigrostrial neurons convert levodopa to dopamine
  • Despite fluctuations in plasma levodopa levels, striatal dopamine is released in a smooth physiological manner

Late Parkinson’s disease

  • Serotonergic neurons convert levodopa to dopamine
  • Fluctuations in plasma levodopa levels lead to fluctuations in striatal dopamine concentrations

What is APO-go INFUSION?

APO-go® INFUSION provides a continuous subcutaneous infusion of apomorphine from a pre-filled syringe delivered using the Crono APO-go III pump.3

Apomorphine infusion can provide a significant and clinically meaningful reduction in OFF time without increasing dyskinesias, and is an effective and well tolerated treatment strategy for patients with Parkinson’s disease whose motor fluctuations are uncontrolled despite optimised oral or transdermal therapy.12

Who is suitable for APO-go® Infusion?

APO-go® INFUSION is indicated for the treatment of motor fluctuations (‘ON-OFF’ phenomena) in patients with Parkinson’s disease which are not sufficiently controlled by oral anti-Parkinson medication.3

The APO-go® INFUSION is suitable for Parkinson’s disease patients with troublesome OFF periods, despite optimized treatment:

  • Patients who consider that rescue doses of APO-go® PEN are required too frequently
  • Where dyskinesias limit further therapy optimisation
  • When non-motor symptoms are associated with OFF periods
  • To simplify complex Parkinson’s disease dosing regimens and improve convenience and compliance with therapy
  • As an alternative to surgical therapy or levodopa-carbidopa intestinal gel (LCIG) if these are contraindicated or because of patient preference
  • When absorption or gastric emptying of oral levodopa is impaired – APO-go INFUSION bypasses the gastrointestinal system9

Key clinical data

The TOLEDO study is the first randomized, double-blind, placebo-controlled, multicentre study of apomorphine subcutaneous infusion in patients with persistent motor fluctuations not optimally controlled with oral or transdermal medications.12

In the TOLEDO study, apomorphine infusion demonstrated:

  • A significant and clinically meaningful mean reduction in OFF time of almost 2 hours compared with placebo. Importantly, this was not achieved at the expense or worsening dyskinesias
    • A similar effect size was seen for the change in ON time without troublesome dyskinesias
  • The treatment effect was comparable to that reported with other infusion therapies, and exceeded that seen with oral or transdermal medications
  • The study showed apomorphine infusion may allow for a reduction in concomitant oral antiparkinsonian medications12

Apomorphine infusion is an effective and well tolerated treatment strategy for patients with Parkinson’s disease whose motor fluctuations are uncontrolled despite optimised oral or transdermal therapy.12


  1. 1. Parkinson’s and You. A guide for people new to the condition. https://www.parkinsons.org.uk/sites/default/files/2018-09/B181%20Parkinson%27s%20and%20you%20WEB.pdf. Accessed 20 Nov 2020.
  2. SmPC: APO-go Pen 10mg/ml Solution for Injection. https://www.medicines.org.uk/emc/product/2232/smpc. Accessed 20 Nov 2020.
  3. 3. SmPC: APO-go PFS 5mg/ml Solution for Infusion in Pre-filled Syringe. https://www.medicines.org.uk/emc/product/3908/smpc. Accessed 20 Nov 2020.
  4. 4. Antonini A & Jenner P. Apomorphine infusion in advanced Parkinson disease. Nat Rev Neurol. 2018;14:693-94.
  5. 5. Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurology 2003;2:107–16
  6. 6. Fasano A, Visanji NP, Liu LWC, et al. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol. 2015;14:625-39.
  7. 7. Stocchi F. The levodopa wearing-off phenomenon in Parkinson’s disease: pharmacokinetic considerations. Exp Opin Pharmacother 2006;7:1399-407.
  8. 8. Chapuis S, Ouchchane L, Metz O, et al. Impact of the motor complications of Parkinson’s disease on the quality of life. Mov Disord. 2005;20:224-30.
  9. 9. Trenkwalder C, Chaudhuri KR, García Ruiz PJ, et al. on behalf of an Expert Consensus Group for the use of apomorphine in Parkinson's disease. Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson's disease - clinical practice recommendations. Parkinsonism Rel Disord 2015;21:1023-30.
  10. 10. Dewey RB Jr, Hutton JT, LeWitt PA, Factor SA. A randomized, double-blind, placebo-controlled trial of subcutaneously injected apomorphine for parkinsonian off-state events. Arch Neurol. 2001;58:1385-92.
  11. 11. Pfeiffer RF, Gutmannb L, Hull KL Jr, et al., the APO302 Study Investigators. Continued efficacy and safety of subcutaneous apomorphine in patients with advanced Parkinson’s disease. Parkinsonism Rel Disord 2007;13:93–100.
  12. 12. Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol 2018;17:749-59.
  13. 13. Silverdale M. Continuous dopaminergic stimulation in Parkinson’s disease. Prog Neurol Psychiatr 2007;11:24-8.
  14. 14. Pietz K, Hagell P, Odin P. J Neurol Neurosurg Psychiatry 1998;65:709–716.
  15. 15. Kanovsky P, et al. Mov Disord 2002;17(1):188–191.


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Parkinson’s UK Website. https://www.parkinsons.org.uk/content/parkinsons-symptoms.

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