Comparative pharmacokinetics of levodopa–carbidopa intestinal gel infusion and foslevodopa–foscarbidopa continuous subcutaneous infusion therapies in advanced Parkinson's disease

INTRODUCTION: Levodopa-carbidopa intestinal gel therapy (LCIG) and foslevodopa-foscarbidopa continuous subcutaneous infusion therapy (FOCS) are device-aided therapies for advanced Parkinson's disease. Comparative real-world pharmacokinetic (PK) data remain limited. This study aimed to compare overall plasma levodopa exposure between LCIG and FOCS. METHODS: Patients who initiated LCIG or FOCS, completed dose optimization, and underwent a standardized levodopa challenge were evaluated. Plasma levodopa concentrations and motor states were assessed repeatedly over 420 min. Overall concentrations were compared using a linear mixed-effects model. Steady-state concentration (SSConc; 300-420 min) and its relationship with body-surface-area-adjusted infusion rate were examined. Time to On and the plasma concentration at On transition (On-Conc) were analyzed. RESULTS: Mean plasma levodopa concentrations tended to be higher with FOCS, although the group effect was not significant (geometric mean ratio: 1.38; p = 0.060). SSConc was higher with FOCS (12.85 ± 2.78 vs. 9.23 ± 1.61 nmol/mL). Both therapies showed linear SSConc-dose relationships, with a steeper slope for FOCS. LCIG produced a faster transition to the On state (median 45 vs. 150 min), whereas On-Conc was similar between groups (approximately 10 nmol/mL). In the FOCS group, baseline Off occurred only when nighttime infusion rates were ≤74 % of daytime rates. CONCLUSION: LCIG and FOCS show distinct PK profiles despite similar overall concentrations. LCIG provides a rapid rise in levodopa levels and earlier On onset, whereas FOCS yields higher SSConc values and greater dose-concentration efficiency, informing titration approaches, nighttime infusion settings, and individualized selection of continuous infusion-based dopaminergic therapy.