| Steady-State Plasma Concentration Profile of Transdermal Rotigotine: An Integrated Analysis of Three, Open-Label, Randomized, Phase I Multiple Dose Studies. | |
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MedLine Citation:
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PMID: 22401642 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background: The dopamine agonist rotigotine is formulated in a transdermal delivery system (patch) for once-daily application. It has been reported as efficacious in the treatment of idiopathic Parkinson's disease (PD) and restless legs syndrome. OBJECTIVE: This article summarizes the results of 3 clinical studies conducted to characterize the 24-hour pharmacokinetic profile of rotigotine in steady state and the effect of different patch application sites on this profile. In addition, the relative bioavailability of a single, large patch versus 2 smaller patches was assessed. METHODS: One Phase I study (SP871) assessed the steady-state pharmacokinetic properties at different application sites at a rotigotine maintenance dose of 3 mg/24 hours in healthy participants. Due to tolerability issues, the steady-state pharmacokinetic properties of rotigotine at higher doses (8 mg/24 hours) was assessed in 2 Phase I studies (SP630, SP651) in early-stage PD patients. Relative rotigotine bioavailability from a 40 cm(2) patch versus 2 × 20 cm(2) patches (SP651) and from a 15 cm(2) patch versus 1 × 5 cm(2) + 1 × 10 cm(2) patches (SP871) was also evaluated. Rotigotine concentrations in plasma were analyzed using a validated LC-MS/MS method. The pharmacokinetic variables were calculated using standard noncompartmental analysis. RESULTS: Release of rotigotine to the skin was 31% to 62% of total drug content in the patch. Variability of rotigotine exposure was low within participants (15%) compared with the variability observed between participants (54%). Rotigotine exposure increased proportionally in the therapeutic dose range of 2 mg/24 hours to 8 mg/24 hours. Plasma concentrations at steady state were stable over the 24-hour patch-on period. Delivery via a single, large patch compared with a combination of smaller patches did not appear to influence exposure to rotigotine. Bioavailability showed some variability depending on patch application site (hip, shoulder, abdomen, flank, thigh, upper arm); the respective mean ratios for AUC ranged between 0.87 (abdomen vs flank) and 1.46 (shoulder vs thigh). CONCLUSIONS: Continuous rotigotine delivery via a once-daily transdermal patch generated stable mean steady-state 24-hour plasma concentrations in healthy participants as well as patients with early-stage PD. Doses were achieved either by application of 1 large patch or a combination of smaller patches, resulting in the same total surface area. |
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Authors:
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Jan-Peer Elshoff; Marina Braun; Jens-Otto Andreas; Michelle Middle; Willi Cawello |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-6 |
Journal Detail:
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Title: Clinical therapeutics Volume: - ISSN: 1879-114X ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7706726 Medline TA: Clin Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved. |
Affiliation:
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UCB Pharma, Monheim am Rhein, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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