Parkinson’s disease is a neurodegenerative disorder that results in the loss of pigmented dopaminergic neurones of the substantia nigra pars compacta, the presence of Lewy bodies and Lewy neuritis. Treatment is symptomatic and is largely aimed at restoring dopamine balance.

There are several treatment options available, with the majority having an effect on dopamine breakdown or acting on dopaminergic receptors. Dopamine agonists act on dopamine receptors whilst levodopa, a precursor of dopamine is administered in combination with a decarboxylase inhibitor to reduce the peripheral decarboxylation of levodopa, thus increasing the amount of levodopa available for transport into the brain. Catechol-O-methyltransferase (COMT) inhibitors act to reduce levodopa breakdown by inhibiting the enzyme COMT, mainly peripherally, to result in an increase in the amount of levodopa available. Monoamine oxidase inhibitors bind to monoamine oxidase type B, an enzyme involved in dopamine metabolism thus reducing its breakdown and also may also inhibit its reuptake. Amantadine, an antiviral agent, is an N-methyl-D-aspartate (NMDA) antagonist with dopaminergic activity as well as anticholinergic effects. Anticholinergics are used in some patients where tremor is problematic; however their use may be limited by their side effects. Treatment for Parkinson’s disease is also aimed at controlling non-motor symptoms, however this will not be discussed within this article.

Intestinal levodopa/carbidopa (ILC) (Duodopa®, Abbvie Pty. Ltd.) is a novel treatment which represents another step forward in the treatment of advanced Parkinson’s disease. Duodopa® is an intestinal gel suspension and is a combination of levodopa and carbidopa. It allows the delivery of the medication by a continuous infusion into the small intestine via a percutaneous endoscopic gastrostomy tubing device with a jejunal tube extension (PEG-J).

The continuous drug delivery (via a CADD-Legacy® pump) into the small intestine reduces variations in the plasma concentration; this results in a steady levodopa concentration and hence a reduction in motor fluctuations, as well as an increase in “on” time. Levodopa is well absorbed from the intestine. The variation in the concentration of levodopa in the plasma is smaller when compared to oral administration as absorption is not affected by the gastric emptying rate given that the medication is delivered directly into the small intestine.

The decision to treat a patient with ILC therapy requires close collaboration between the neurologist and a gastroenterologist and should only be commenced in a hospital setting. The initiation of therapy involves a two phase process – the nasojejunal phase and the PEG-J phase.

The initial nasojejunal phase involves the insertion of a temporary, naso-intestinal tube and ILC is delivered directly into the jejenum. The recommended trial phase is three to five days and is aimed at assessing the clinical response to ILC, as well as determining the optimal dose for the patient which maximises the functional “on” time during the day.

Following a positive clinical response to ILC, the second phase involves the insertion of a PEG-J tube to allow long term administration.

In Australia, Duodopa® is indicated for the treatment of advanced idiopathic Parkinson’s disease with severe motor fluctuations despite optimised alternative pharmacological treatment and is currently listed on the Pharmaceutical Benefits Scheme. It is an expensive treatment which costs approximately $6,000.00 per month, however the treatment is estimated to be applicable to only 2,000 patients. Consumption has already reached $10 million of the forecasted cost of $10 million to $30 million by 2017. Despite its high cost and specific indication, ILC provides yet another option for prescribers in the treatment of advanced Parkinson’s disease to improve quality of life and reduce the burden for carers.

References:

  1. Abbvie Pty Ltd. Duodopa® Resource Guide for Hospitals. Botany: Abbvie Pty Ltd; 2013.
  2. Hauser RA, Lyons KE, McClain TA, Pahwa R. Drugs and Diseases: Parkinson Disease. New York: WebMD LLC; 2014. Accessed 13/06/2014.
  3. Lindsay KW, Bone I. Neurology and Neurosurgery Illustrated. 4th ed. London: Churchill Livingstone; 2004. p. 359-64.
  4. Olanow C, Schapira AV. Parkinson’s Disease and Other Movement Disorders. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. editors. Harrison’s Principles of Internal Medicine, 18th ed. New York: McGraw-Hill; 2012.
  5. Rossi S (ed). Australian Medicines Handbook 2014 (online). Adelaide: Australian Medicines Handbook Pty Ltd; 2014 July. Available from: http://www.amh.net.au.

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