Objectives. To characterize the pharmacokinetic profile of
levodopa (
L-dopa) and
carbidopa after repeated doses of the effervescent
tablet of
melevodopa/
carbidopa (V1512;
Sirio) compared with standard-release
L-dopa/
carbidopa in patients with fluctuating
Parkinson's disease. Few studies assessed the pharmacokinetics of
carbidopa to date. Methods. This was a single-centre, randomized, double-blind, double-dummy, two-period crossover study. Patients received V1512 (
melevodopa 100 mg/
carbidopa 25 mg) or
L-dopa 100 mg/
carbidopa 25 mg, 7 doses over 24 hours (Cohort 1), 4 doses over 12 hours (Cohort 2), or 2 doses over 12 hours in combination with
entacapone 200 mg (Cohort 3). Pharmacokinetic parameters included area under the plasma-concentration time curve (AUC), maximum plasma concentration (C max), and time to C max (t max). Results. Twenty-five patients received at least one dose of study medication.
L-dopa absorption tended to be quicker and pharmacokinetic parameters less variable after V1512 versus
L-dopa/
carbidopa, both over time and between patients. Accumulation of
L-dopa in plasma was less noticeable with V1512.
Carbidopa exposure and interpatient variability was lower when V1512 or
L-dopa/
carbidopa was given in combination with
entacapone. Both treatments were well tolerated. Conclusions. V1512 provides a more reliable
L-dopa pharmacokinetic profile versus standard-release
L-dopa/
carbidopa, with less
drug accumulation and less variability. This trial is registered with ClinicalTrials.gov NCT00491998.