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Pharmacokinetics of Rytary(®), An Extended-Release Capsule Formulation of Carbidopa–Levodopa
Parkinson’s disease (PD) is a chronic progressive neurological disorder characterized by resting tremor, rigidity, bradykinesia, gait disturbance, and postural instability. Levodopa, the precursor to dopamine, coadministered with carbidopa or benserazide, aromatic amino acid decarboxylase inhibitors...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer International Publishing
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563351/ https://www.ncbi.nlm.nih.gov/pubmed/28236251 http://dx.doi.org/10.1007/s40262-017-0511-y |
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author | Mittur, Aravind Gupta, Suneel Modi, Nishit B. |
author_facet | Mittur, Aravind Gupta, Suneel Modi, Nishit B. |
author_sort | Mittur, Aravind |
collection | PubMed |
description | Parkinson’s disease (PD) is a chronic progressive neurological disorder characterized by resting tremor, rigidity, bradykinesia, gait disturbance, and postural instability. Levodopa, the precursor to dopamine, coadministered with carbidopa or benserazide, aromatic amino acid decarboxylase inhibitors, is the most effective and widely used therapeutic agent in the treatment of PD. With continued levodopa treatment, a majority of patients develop motor complications such as dyskinesia and motor ‘on-off’ fluctuations, which are, in part, related to the fluctuations in plasma concentrations of levodopa. A new extended-release (ER) carbidopa–levodopa capsule product (also referred to as IPX066) was developed and approved in the US as Rytary(®) and in the EU as Numient(®). The capsule formulation is designed to provide an initial rapid absorption of levodopa comparable to immediate-release (IR) carbidopa–levodopa, and to subsequently provide stable levodopa concentrations with reduced peak-to-trough excursions in plasma concentrations in order to reduce motor fluctuations associated with pulsatile stimulation of dopamine receptors and to minimize dyskinesia. Phase III studies of this ER carbidopa–levodopa capsule formulation in patients with PD have shown a significant reduction in ‘off’ time compared with IR carbidopa–levodopa and carbidopa–levodopa–entacapone. We present a review of the clinical pharmacokinetics and pharmacodynamics of this ER product of carbidopa–levodopa in healthy subjects and in patients with PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40262-017-0511-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5563351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-55633512017-09-01 Pharmacokinetics of Rytary(®), An Extended-Release Capsule Formulation of Carbidopa–Levodopa Mittur, Aravind Gupta, Suneel Modi, Nishit B. Clin Pharmacokinet Review Article Parkinson’s disease (PD) is a chronic progressive neurological disorder characterized by resting tremor, rigidity, bradykinesia, gait disturbance, and postural instability. Levodopa, the precursor to dopamine, coadministered with carbidopa or benserazide, aromatic amino acid decarboxylase inhibitors, is the most effective and widely used therapeutic agent in the treatment of PD. With continued levodopa treatment, a majority of patients develop motor complications such as dyskinesia and motor ‘on-off’ fluctuations, which are, in part, related to the fluctuations in plasma concentrations of levodopa. A new extended-release (ER) carbidopa–levodopa capsule product (also referred to as IPX066) was developed and approved in the US as Rytary(®) and in the EU as Numient(®). The capsule formulation is designed to provide an initial rapid absorption of levodopa comparable to immediate-release (IR) carbidopa–levodopa, and to subsequently provide stable levodopa concentrations with reduced peak-to-trough excursions in plasma concentrations in order to reduce motor fluctuations associated with pulsatile stimulation of dopamine receptors and to minimize dyskinesia. Phase III studies of this ER carbidopa–levodopa capsule formulation in patients with PD have shown a significant reduction in ‘off’ time compared with IR carbidopa–levodopa and carbidopa–levodopa–entacapone. We present a review of the clinical pharmacokinetics and pharmacodynamics of this ER product of carbidopa–levodopa in healthy subjects and in patients with PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40262-017-0511-y) contains supplementary material, which is available to authorized users. Springer International Publishing 2017-02-24 2017 /pmc/articles/PMC5563351/ /pubmed/28236251 http://dx.doi.org/10.1007/s40262-017-0511-y Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Review Article Mittur, Aravind Gupta, Suneel Modi, Nishit B. Pharmacokinetics of Rytary(®), An Extended-Release Capsule Formulation of Carbidopa–Levodopa |
title | Pharmacokinetics of Rytary(®), An Extended-Release Capsule Formulation of Carbidopa–Levodopa |
title_full | Pharmacokinetics of Rytary(®), An Extended-Release Capsule Formulation of Carbidopa–Levodopa |
title_fullStr | Pharmacokinetics of Rytary(®), An Extended-Release Capsule Formulation of Carbidopa–Levodopa |
title_full_unstemmed | Pharmacokinetics of Rytary(®), An Extended-Release Capsule Formulation of Carbidopa–Levodopa |
title_short | Pharmacokinetics of Rytary(®), An Extended-Release Capsule Formulation of Carbidopa–Levodopa |
title_sort | pharmacokinetics of rytary(®), an extended-release capsule formulation of carbidopa–levodopa |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563351/ https://www.ncbi.nlm.nih.gov/pubmed/28236251 http://dx.doi.org/10.1007/s40262-017-0511-y |
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