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Parkinson’s Disease
Volume 2015, Article ID 369465, 7 pages
http://dx.doi.org/10.1155/2015/369465
Clinical Study

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

1Institute of Neurology, IRCCS San Raffaele, Via della Pisana 235, 00163 Rome, Italy
2Vernalis (R&D) Ltd., Reading Road, Winnersh, Berkshire RG41 5UA, UK
3Chiesi Farmaceutici SpA, 43100 Parma, Italy

Received 12 March 2015; Revised 5 May 2015; Accepted 18 May 2015

Academic Editor: Jan O. Aasly

Copyright © 2015 Fabrizio Stocchi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 (), and time to (). 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.