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Information |
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Drug Groups
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approved; investigational |
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Description
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Rotigotine (Neupro) is a non-ergoline dopamine agonist indicated for the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS) in Europe and the United States. It is formulated as a once-daily transdermal patch which provides a slow and constant supply of the drug over the course of 24 hours.
Like other dopamine agonists, rotigotine has been shown to possess antidepressant effects and may be useful in the treatment of depression as well.
Rotigotine was developed by Aderis Pharmaceuticals. In 1998, Aderis licensed worldwide development and commercialization rights for rotigotine to the German pharmaceutical company Schwarz Pharma (today a subsidiary of the Belgian company UCB S.A.). The drug has been approved by the EMEA for use in Europe in 2006 and is today being sold in several European countries. In 2007, the Neupro patch was approved by the Food and Drug Administration (FDA) as the first transdermal treatment of Parkinson's disease in the United States. However, as of 2008, Schwarz Pharma has recalled all Neupro patches in the United States and some in Europe because of problems with the delivery mechanism. Rotigotine has been authorized as a treatment for RLS since August 2008. |
| Indication |
For use/treatment in neurologic disorders and parkinson's disease as well as moderate-to-severe primary Restless Legs Syndrome. |
| Pharmacology |
There is no indication of a QT/QTc prolonging effect of Neupro in doses up to 24 mg/24 hours. The effects of Neupro at doses up to 24 mg/24 hours (supratherapeutic doses) on the QT/QTc interval was evaluated in a double-blind, randomized, placebo- and positive-controlled (moxifloxacin 400 mg IV, single dose) parallel-group trial with an overall treatment period of 52 days in male and female patients with advanced-stage Parkinson's disease. Assay sensitivity was confirmed by significant QTc prolongation by moxifloxacin. |
| Toxicity |
The most likely symptoms of overdose would be those related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, hypotension, involuntary movements, hallucinations, confusion, convulsions, and other signs of excessive dopaminergic stimulation. |
| Biotransformation |
Hepatic (CYP-mediated). |
| Absorption |
Bioavailability is 37% (transdermal) |
| Half Life |
After removal of the patch, plasma levels decreased with a terminal half-life of 5 to 7 hours. The pharmacokinetic profile showed a biphasic elimination with an initial half-life of 3 hours. |
| Protein Binding |
92 % in vitro and 89.5 % in vivo. Rotigotine is extensively metabolized by conjugation and N-dealkylation. After intravenous dosing the predominant metabolites in human plasma are sulfate conjugates of rotigotine, glucuronide conjugates of rotigotine, sulfate conjugates of the N-despropyl-rotigotine and conjugates of N-desthienylethyl-rotigotine. Multiple CYP isoenzymes, sulfotransferases and two UDP-glucuronosyltransferases catalyze the metabolism of rotigotine. |
| Elimination |
Urine (71%), Fecal (23%) |
| Distribution |
The weight normalized apparent volume of distribution, (Vd/F), in humans is approximately 84 L/kg after repeated dose administration. |
| References |
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Giladi N, Boroojerdi B, Korczyn AD, Burn DJ, Clarke CE, Schapira AH: Rotigotine transdermal patch in early Parkinson's disease: A randomized, double-blind, controlled study versus placebo and ropinirole. Mov Disord. 2007 Oct 12;.
[Pubmed]
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Chen JJ, Swope DM, Dashtipour K, Lyons KE: Transdermal rotigotine: a clinically innovative dopamine-receptor agonist for the management of Parkinson's disease. Pharmacotherapy. 2009 Dec;29(12):1452-67.
[Pubmed]
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