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Because maintaining effective levels of levodopa remains challenging, there is interest in developing continuous-delivery systems for Parkinson disease (PD) medications. In this manufacturer-sponsored study, investigators tested the subcutaneous soluble levodopa/carbidopa phosphate prodrug foslevodopa/foscarbidopa (ABBV-951) for equilibrium solubility and chemical stability, delivered subcutaneously via a continuous-delivery infusion pump. They tested solutions of pH-adjusted lyophilized materials in water with ratios of foslevodopa to foscarbidopa ranging from 4:1 to 20:1. The solutions were infused into 21 healthy volunteers.
ABBV-951 had high water solubility and chemical stability at physiologic pH. Following infusion in healthy individuals, a stable levodopa pharmacokinetic profile was achieved and maintained for ≤72 hours. The approach was safe and tolerable.
Rosebraugh M et al. Foslevodopa/foscarbidopa: A new subcutaneous treatment for Parkinson's disease. Ann Neurol 2021 Mar 26; [e-pub]. (https://doi.org/10.1002/ana.26073)
Comment
Delivering levodopa across the skin has been a formidable challenge. Continuous levodopa delivery through a subcutaneous approach using selective levodopa monophosphate synthesis is novel. The authors suggest that this type of approach should meet the following criteria: “(1) high aqueous solubility, (2) excellent chemical stability, and (3) highly efficient conversion of the water-soluble salt or prodrug to the active pharmaceutical ingredient.” A phase 2 study in a PD population will be the next step for this approach. The reduction in pill burden without the invasiveness of brain surgery or duodenal tube placement could make this therapy of interest to people with PD.