Foslevodopa/foscarbidopa subcutaneous infusion maintains equivalent levodopa exposure to levodopa-carbidopa intestinal gel delivered to the jejunum

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals

“…Subcutaneous foslevodopa/foscarbidopa infusion: We found no studies explicitly stating LED conversion formula for subcutaneous foslevodopa/foscarbidopa infusion. However, we appraised a pharmacokinetic study with crossover design which reported similar levodopa exposures after subcutaneous infusion of foslevodopa/foscarbidopa 700/35 mg compared to intrajejunal infusion of levodopa/carbidopa 350/87.5 mg followed by two doses of oral levodopa/carbidopa 100/25 mg 29 Opicapone and other COMT inhibitors: The LED conversion formula for opicapone proposed here is in line with two previous publications 30,31 .…”

Metabolite profiling of foslevodopa/foscarbidopa in plasma of healthy human participants by LC‐HRMS indicates no major differences compared to administration of levodopa/carbidopa intestinal gel

“…Continuing the discussion set forth by Rosebraugh et al regarding the safety of foslevodopa/foscarbidopa,21 our results are additionally auspicious. Having now shown similar LD exposure, similar human safety results, and similar metabolite profiles between foslevodopa/foscarbidopa and LCIG, it would seem unlikely for safety concerns to arise with foslevodopa/foscarbidopa that have not already been identified with LCIG.…”

“…foslevodopa/foscarbidopa to be a viable alternative to LCIG, it must provide similar exposures of LD to that observed after LCIG administration. A series of three papers by Rosebraugh et al has demonstrated the achievement of that desired similar exposure in humans: (1) Foslevodopa/foscarbidopa was infused subcutaneously at four different rates in Parkinsonian patients and the desired exposure of LD was achieved 32 ; (2) With foslevodopa/ foscarbidopa subcutaneous infusion in healthy participants, the ratio of foslevodopa/foscarbidopa required to yield the desired exposure of LD was determined 20 ; (3) Foslevodopa/foscarbidopa subcutaneous infusion was compared directly to LCIG jejunal 16-h infusion in healthy participants and comparable LD expo-sure was demonstrated during the LCIG infusion period 21. In that Mean levodopa plasma concentrations following infusions of LCIG and foslevodopa/foscarbidopa.…”

Infusion Therapies in the Treatment of Parkinson’s Disease

“…Foslevodopa/foscarbidopa (previously known and referred to as ABBV-951) is a new soluble formulation of carbidopa and levodopa prodrugs delivered as a 24-hour/day continuous subcutaneous infusion by an infusion set connected to a portable pump [52][53][54]. On delivery to the body, foslevodopa/foscarbidopa is rapidly converted to the pharmacologically active levodopa/carbidopa via alkaline phosphatases, quickly reaching and maintaining steady-state therapeutic levels of plasma levodopa [52].…”