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Improving the Delivery of Levodopa in Parkinson’s Disease: A Review of Approved and Emerging Therapies

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Abstract

Levodopa is the most effective drug for the treatment of Parkinson’s disease, but its use as an oral medication is complicated by its erratic absorption, extensive metabolism and short plasma half-life. On long-term use and with disease progression, there is a high incidence of motor and non-motor complications, which remain a major clinical and research challenge. It is widely accepted that levodopa needs to be administered using formulations that result in good and consistent bioavailability and the physiologically relevant and continuous formation of dopamine in the brain to maximise its efficacy while avoiding and reversing ‘wearing off’ and dyskinesia. However, the physicochemical properties of levodopa along with its pharmacokinetic and pharmacodynamic profile make it difficult to deliver the drug in a manner that fulfils these criteria. In this review, we examine the problems associated with the administration of levodopa in Parkinson’s disease and how the use of novel technologies and delivery devices is leading to a more consistent and sustained levodopa delivery with the aim of controlling motor function as well as non-motor symptoms.

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Acknowledgements

The authors thank Pierpaolo Urso for graphical assistance with the figure.

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  1. Daniele Urso and K. Ray Chaudhuri and are joint first authors.

Authors and Affiliations

  1. Department of Neurosciences, King’s College London, Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, London, SE5 8AF, UK

    Daniele Urso, K. Ray Chaudhuri & Mubasher A. Qamar

  2. Parkinson’s Foundation Centre of Excellence, King’s College Hospital, Denmark Hill, London, UK

    Daniele Urso, K. Ray Chaudhuri & Mubasher A. Qamar

  3. Institute of Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King’s College, London, UK

    Peter Jenner

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  1. Daniele Urso
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Correspondence to Daniele Urso.

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Daniele Urso, K. Ray Chaudhuri, Mubasher A. Qamar and Peter Jenner have no conflicts of interest that are directly relevant to the content of this article.

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DU, KRC and PJ conceptualised the paper and drafted and revised the manuscript. MAQ drafted and revised the manuscript. All authors approved the final manuscript.

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Urso, D., Chaudhuri, K.R., Qamar, M.A. et al. Improving the Delivery of Levodopa in Parkinson’s Disease: A Review of Approved and Emerging Therapies. CNS Drugs 34, 1149–1163 (2020). https://doi.org/10.1007/s40263-020-00769-7

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