L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson’s Disease: A Randomised Study
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...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2015/369465 |
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| author | Fabrizio Stocchi Laura Vacca Paola Grassini Stephen Pawsey Holly Whale Stefano Marconi Margherita Torti |
| author_facet | Fabrizio Stocchi Laura Vacca Paola Grassini Stephen Pawsey Holly Whale Stefano Marconi Margherita Torti |
| author_sort | Fabrizio Stocchi |
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| description | 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 (Cmax), and time to Cmax (tmax). 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. |
| format | Article |
| id | doaj-art-6ee4b316834c4da7b59d9329b29a8da6 |
| institution | Kabale University |
| issn | 2090-8083 2042-0080 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-6ee4b316834c4da7b59d9329b29a8da62025-02-03T00:59:59ZengWileyParkinson's Disease2090-80832042-00802015-01-01201510.1155/2015/369465369465L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson’s Disease: A Randomised StudyFabrizio Stocchi0Laura Vacca1Paola Grassini2Stephen Pawsey3Holly Whale4Stefano Marconi5Margherita Torti6Institute of Neurology, IRCCS San Raffaele, Via della Pisana 235, 00163 Rome, ItalyInstitute of Neurology, IRCCS San Raffaele, Via della Pisana 235, 00163 Rome, ItalyInstitute of Neurology, IRCCS San Raffaele, Via della Pisana 235, 00163 Rome, ItalyVernalis (R&D) Ltd., Reading Road, Winnersh, Berkshire RG41 5UA, UKVernalis (R&D) Ltd., Reading Road, Winnersh, Berkshire RG41 5UA, UKChiesi Farmaceutici SpA, 43100 Parma, ItalyInstitute of Neurology, IRCCS San Raffaele, Via della Pisana 235, 00163 Rome, ItalyObjectives. 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 (Cmax), and time to Cmax (tmax). 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.http://dx.doi.org/10.1155/2015/369465 |
| spellingShingle | Fabrizio Stocchi Laura Vacca Paola Grassini Stephen Pawsey Holly Whale Stefano Marconi Margherita Torti L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson’s Disease: A Randomised Study Parkinson's Disease |
| title | L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson’s Disease: A Randomised Study |
| title_full | L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson’s Disease: A Randomised Study |
| title_fullStr | L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson’s Disease: A Randomised Study |
| title_full_unstemmed | L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson’s Disease: A Randomised Study |
| title_short | L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson’s Disease: A Randomised Study |
| title_sort | l dopa pharmacokinetic profile with effervescent melevodopa carbidopa versus standard release levodopa carbidopa tablets in parkinson s disease a randomised study |
| url | http://dx.doi.org/10.1155/2015/369465 |
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