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Continuous Drug Delivery in Parkinson’s Disease

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Abstract

Development of motor and non-motor complications during the course of Parkinson’s disease (PD) is a major challenge for therapeutic management. At advanced disease stages, patients frequently fluctuate between PD symptoms–such as bradykinesia–and dyskinesias, in response to fluctuations in drug concentrations. Continuous subcutaneous infusion of the dopamine agonist apomorphine or intestinal infusion of levodopa reduce such fluctuations in both pharmacokinetics and motor function. This is the basis for the concept of continuous drug delivery in PD, and the more theoretical concept of continuous dopaminergic stimulation. These expressions are sometimes used to describe a treatment that is more continuous in its pharmacokinetic profile or that produces more sustained effects, compared with immediate-release levodopa, i.e. not only pump treatments. For example, sustained-release formulations of levodopa or dopamine agonists, transdermal delivery of rotigotine, and addition of catechol-O-methyltransferase inhibitors or monoamine oxidase-B inhibitors have been developed with the aim to provide more continuous drug concentrations, sustained benefits and minimized side effects. Progress has been made, but there are still knowledge gaps regarding how these treatment alternatives can be optimally used. New treatments are currently being developed to provide the continuous drug delivery that is known to successfully alleviate motor and non-motor complications. Hopefully, although not yet proven, these new methods may also prevent or postpone some of the late-stage complications.

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Acknowledgments

There was no funding for writing this manuscript. Marina Senek reports no conflicts of interest. Dag Nyholm receives royalties from Liber AB; has served as a consultant to AbbVie, AstraZeneca and Sensidose AB; has received honoraria from H. Lundbeck AB and NordicInfu Care; has received research support from Kibion AB, Selanders Foundation, Swedish Knowledge Foundation, Swedish Parkinson’s Disease Foundation and Swedish Research Council; is a co-founder and stock owner in Jemardator AB; receives remuneration from the website netdoktor.se for participation in an expert panel; received postdoctoral support from the Swedish Society for Medical Research; and received institutional postdoctoral support from Uppsala University.

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  1. Department of Neuroscience, Neurology, Uppsala University, SE-75185, Uppsala, Sweden

    Marina Senek & Dag Nyholm

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  1. Marina Senek
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  2. Dag Nyholm
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Correspondence to Dag Nyholm.

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Senek, M., Nyholm, D. Continuous Drug Delivery in Parkinson’s Disease. CNS Drugs 28, 19–27 (2014). https://doi.org/10.1007/s40263-013-0127-1

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