Objective: To characterize the pharmacokinetics (PK) of levodopa (LD) after bolus delivery of foslevodopa/foscarbidopa

Background: Foslevodopa/foscarbidopa is a soluble formulation of LD/CD prodrugs delivered as a continuous (24-hour/day) subcutaneous infusion, which provides consistent therapeutic levels of LD, mitigating the shortcomings of the progressive reduced effectiveness of oral LD in advanced Parkison’s disease. To reach effective LD exposures more rapidly, patients can be administered a bolus SC dose of foslevodopa/foscarbidopa followed by a continuous SC infusion.  Additionally, small bolus doses (extra doses) can be administered during the continuous infusion to optimize symptomatic control.  The current work characterizes the LD PK following foslevodopa/foscarbidopa SC bolus administration.

Method: Single 200 mg SC bolus dose of foslevodopa/foscarbidopa was administered in the abdomen in 12 healthy volunteers over 1 minute. Serial plasma samples were collected to assay for LD and CD concentrations. Safety and tolerability were assessed throughout the study. PK parameters including C_max AUC, T_max, and t_1/2 were computed.

PopPK model was developed based on LD and CD concentration data across multiple studies. Simulations of the LD and CD PK profile after or without administration of bolus dose followed by a constant infusion rate were performed and time to steady state was assessed.

Results: After single SC bolus dose, the foslevodopa/foscarbidopa was rapidly absorbed and converted to CD and LD. The median T_max of LD and CD were 1.3 h and 1.5 h, respectively.

Treatment Emergent adverse events (AEs) in healthy volunteers were non-serious and mild in severity including skin related AEs.

The simulation of the LD and CD PK showed that with initial bolus dose administration, steady state could be achieved within 2 hours, which is significantly faster than through constant infusion only.

Conclusion: Initial bolus administration of foslevodopa/foscarbidopa can be used to quickly achieve LD steady state when combined with a continuous infusion.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pharmacokinetics-of-levodopa-after-subcutaneous-bolus-delivery-of-foslevodopa-foscarbidopa/