title: 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.
authors.affiliation: Institute of Neurology, IRCCS San Raffaele, Via della Pisana 235, 00163 Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Stocchi
authors.affiliation: Institute of Neurology, IRCCS San Raffaele, Via della Pisana 235, 00163 Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Vacca
authors.affiliation: Institute of Neurology, IRCCS San Raffaele, Via della Pisana 235, 00163 Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Grassini
authors.affiliation: Vernalis (R&D) Ltd., Reading Road, Winnersh, Berkshire RG41 5UA, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Pawsey
authors.affiliation: Vernalis (R&D) Ltd., Reading Road, Winnersh, Berkshire RG41 5UA, UK.
authors.forename: Holly
authors.initials: H
authors.lastname: Whale
authors.affiliation: Chiesi Farmaceutici SpA, 43100 Parma, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Marconi
authors.affiliation: Institute of Neurology, IRCCS San Raffaele, Via della Pisana 235, 00163 Rome, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Torti