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Behavioral and neurophysiological effects of transdermal rotigotine in atypical parkinsonism.

ABSTRACT: Effective therapies for the so-called atypical parkinsonian syndrome (APS) such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome (CBS) are not available. Dopamine agonists (DA) are not often used in APS because of inefficacy and in a minority of case, their side effects, like dyskinesias, impairment of extrapyramidal symptoms or the appearance of psychosis, and REM sleep behavioral disorders (RBD). Transdermal rotigotine (RTG) is a non-ergot dopamine agonist indicated for use in early and advanced Parkinson's disease with a good tolerability and safety. Moreover, its action on a wide range of dopamine receptors, D1, D2, D3, unlike other DA, could make it a good option in APS, where a massive dopamine cell loss is documented. In this pilot, observational open-label study we evaluate the efficacy and tolerability of RTG in patients affected by APS. Thirty-two subjects with diagnosis of APS were treated with transdermal RTG. APS diagnosis was: MSA parkinsonian type (MSA-P), MSA cerebellar type (MSA-C), PSP, and CBS. Patients were evaluated by UPDRS-III, neuropsychiatric inventory, mini mental state examination at baseline, and after 6, 12, and 18?months. The titration schedule was maintained very flexible, searching the major clinical effect and the minor possible adverse events (AEs) at each visit. AEs were recorded. APS patients treated with RTG show an overall decrease of UPDRS-III scores without increasing behavioral disturbances. Only three patients were dropped out of the study. Main AEs were hypotension, nausea, vomiting, drowsiness, and tachycardia. The electroencephalographic recording power spectra analysis shows a decrease of theta and an increase of low alpha power. In conclusion, transdermal RTG seems to be effective and well tolerated in APS patients.

SUBMITTER: Moretti DV

PROVIDER: S-EPMC4046164 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Behavioral and neurophysiological effects of transdermal rotigotine in atypical parkinsonism.

Moretti Davide Vito DV Binetti Giuliano G Zanetti Orazio O Frisoni Giovanni Battista GB Frisoni Giovanni Battista GB

Frontiers in neurology 20140605

Effective therapies for the so-called atypical parkinsonian syndrome (APS) such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome (CBS) are not available. Dopamine agonists (DA) are not often used in APS because of inefficacy and in a minority of case, their side effects, like dyskinesias, impairment of extrapyramidal symptoms or the appearance of psychosis, and REM sleep behavioral disorders (RBD). Transdermal rotigotine (RTG) is a non-ergot dopami ...[more]

PMID: 24926284

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Project description:Immobilisation, blood loss, sleep deficiency, and (concomitant) medications during perioperative periods might lead to acute exacerbation of symptoms in patients with the restless legs syndrome (RLS). Continuous transdermal delivery of the dopamine agonist rotigotine provides stable plasma levels over 24 h and may provide RLS patients with a feasible treatment option for perioperative situations. To assess the feasibility of use of rotigotine transdermal patch for the perioperative management of moderate to severe RLS, long-term data of an open-label extension of a rotigotine dose-finding study were retrospectively reviewed.The data of all 295 patients who had entered the 5-year study were screened independently by two reviewers for the occurrence of surgical interventions during the study period. The following data were included in this post-hoc analysis: patient age, sex, surgical intervention and outcome, duration of hospital stay, rotigotine maintenance dose at the time of surgery, rotigotine dose adjustment, and continuation/discontinuation of rotigotine treatment. All parameters were analysed descriptively. No pre-specified efficacy assessments (e.g. IRLS scores) were available for the perioperative period.During the study period, 61 surgical interventions were reported for 52 patients (median age, 63 years; 67% female); the majority of patients (85%) had one surgical intervention. The mean rotigotine maintenance dose at time of surgery was 3.1?±?1.1 mg/24 h. For most interventions (95%), rotigotine dosing regimens were maintained during the perioperative period. Administration was temporarily suspended in one patient and permanently discontinued in another two. The majority (96%) of the patients undergoing surgery remained in the study following the perioperative period and 30 of these patients (61%) completed the 5-year study.Although the data were obtained from a study which was not designed to assess rotigotine use in the perioperative setting, this post-hoc analysis suggests that treatment with rotigotine transdermal patch can be maintained during the perioperative period in the majority of patients and may allow for uninterrupted alleviation of RLS symptoms.The 5-year rotigotine extension study is registered with ClinicalTrials.gov, identifier NCT00498186.

Project description:Background and objectivesRotigotine is a dopamine receptor agonist with activity across the D1 through to D5 receptors as well as select serotonergic and adrenergic sites; continuous transdermal delivery of rotigotine with replacement of the patch once daily maintains stable plasma concentrations over 24 h. Rotigotine is indicated for the treatment of early and advanced-stage Parkinson's disease and moderate-to-severe idiopathic restless legs syndrome. The pharmacokinetics and pharmacodynamics of a drug may vary between subjects of different ethnic origin. This study evaluated the pharmacokinetics, safety, and tolerability of single-dose treatment with rotigotine transdermal patch in Japanese and Caucasian subjects.MethodsIn this open-label, parallel-group study, healthy male and female subjects of Japanese or Caucasian ethnic origin were matched by sex, body mass index, and age. A single transdermal patch delivering 2 mg/24 h rotigotine (patch content 4.5 mg) was applied to the ventral/lateral abdomen for 24 h. The main outcome measures were the plasma concentrations of unconjugated and total rotigotine and its desalkyl metabolites and derived pharmacokinetic parameters (area under the concentration-time curve from time zero to last quantifiable concentration [AUClast], maximum plasma concentration [Cmax], and body weight- and dose-normalized values).ResultsThe pharmacokinetic analysis included 48 subjects (24 Japanese, 24 Caucasian). The mean apparent dose of rotigotine was 2.0±0.5 mg for Japanese subjects and 2.08±0.58 mg for Caucasians. Plasma concentration-time profiles of unconjugated rotigotine and of the main metabolites were similar for both ethnic groups. Parameters of model-independent pharmacokinetics, Cmax, time to Cmax (tmax), and AUClast, for unconjugated rotigotine showed no statistically significant differences between Japanese and Caucasian subjects. Values of concentration-dependent pharmacokinetic parameters were higher in female subjects; this difference was minimized after correction for body weight. A statistically significant difference between ethnic groups was observed for total rotigotine concentrations (total rotigotine=unconjugated rotigotine+conjugated rotigotine), with slightly lower values in Caucasians after correction for body weight and apparent dose. No relevant differences were observed between males and females. Inter-individual variability was high. The terminal half-life for unconjugated rotigotine was 5.3 h in Japanese subjects and 5.7 h in Caucasians; corresponding values for total rotigotine were 8.6 h and 9.6 h. Less than 0.1% of the apparent dose was renally excreted as the parent compound. Renal elimination of total rotigotine covers 11.7% of absorbed dose in Japanese subjects and 10.8% of the absorbed dose in Caucasians, whereas the renal elimination via total despropyl rotigotine was 8.2 and 7.1%, respectively. The corresponding values for total desthienylethyl rotigotine were 3.5% in Japanese subjects and 4.2% Caucasians. Most adverse events were mild in intensity and typical for dopamine agonists or for transdermal therapeutics.ConclusionAdministration of a single patch delivering 2 mg/24 h rotigotine resulted in comparable pharmacokinetic profiles in Japanese and Caucasian subjects. The rotigotine transdermal patch was generally well-tolerated. Our findings suggest similar dose requirements for Japanese and Caucasian populations.

Dataset Information

Behavioral and neurophysiological effects of transdermal rotigotine in atypical parkinsonism.

Publications

Behavioral and neurophysiological effects of transdermal rotigotine in atypical parkinsonism.

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