L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson's Disease: A Randomised Study

Abstract

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.

Figures

Figure 1

L-dopa plasma concentrations for patients in Cohort 1 (dose administration every 2 hours) receiving V1512 solution (a) or L-dopa/carbidopa 100/25 mg standard-release tablets (b). All patients with data available for the pharmacokinetic analyses were included; patients with significant violations that may have invalidated or biased the results of the pharmacokinetic evaluations were excluded. –·–·–· = lower limit of quantification (10 ng/mL).

Figure 2

L-dopa plasma concentrations for patients in Cohort 2 (dose administration every 3 hours) receiving V1512 solution (a) or L-dopa/carbidopa 100/25 mg standard-release tablets (b). All patients with data available for the pharmacokinetic analyses were included; patients with significant violations that may have invalidated or biased the results of the pharmacokinetic evaluations were excluded. –·–·–· = lower limit of quantification (10 ng/mL).

Figure 3

L-dopa plasma concentrations for patients in Cohort 3 (dose administration every 3 hours) receiving V1512 solution plus entacapone 200 mg (a) or L-dopa/carbidopa 100/25 mg standard-release tablets plus entacapone 200 mg (b). All patients with data available for the pharmacokinetic analyses were included; patients with significant violations that may have invalidated or biased the results of the pharmacokinetic evaluations were excluded. –·–·–· = lower limit of quantification (10 ng/mL).