An update on pharmacological, pharmacokinetic properties and drug-drug interactions of rotigotine transdermal system in Parkinson's disease and restless legs syndrome

Drugs. 2015 Apr;75(5):487-501. doi: 10.1007/s40265-015-0377-y.

Abstract

This narrative review reports on the pharmacological and pharmacokinetic properties of rotigotine, a non-ergolinic D₃/D₂/D₁ dopamine receptor agonist approved for the treatment of early- and advanced-stage Parkinson's disease (PD) and moderate to severe restless legs syndrome (RLS). Rotigotine is formulated as a transdermal patch providing continuous drug delivery over 24 h, with a plasma concentration profile similar to that of administration via continuous intravenous infusion. Absolute bioavailability after 24 h transdermal delivery is 37 % of the applied rotigotine dose. Following a single administration of rotigotine transdermal system (24-h patch-on period), most of the absorbed drug is eliminated in urine and feces as sulphated and glucuronidated conjugates within 24 h of patch removal. The drug shows a high apparent volume of distribution (>2500 L) and a total body clearance of 300-600 L/h. Rotigotine transdermal system provides dose-proportional pharmacokinetics up to supratherapeutic dose rates of 24 mg/24 h, with steady-state plasma drug concentrations attained within 1-2 days of daily dosing. The pharmacokinetics of rotigotine transdermal patch are similar in healthy subjects, patients with early- or advanced-stage PD, and patients with RLS when comparing dose-normalized area under the plasma concentration-time curve (AUC) and maximum plasma drug concentration (Cmax), as well as half-life and other pharmacokinetic parameters. Also, it is not influenced in a relevant manner by age, sex, ethnicity, advanced renal insufficiency, or moderate hepatic impairment. No clinically relevant drug-drug interactions were observed following co-administration of rotigotine with levodopa/carbidopa, domperidone, or the CYP450 inhibitors cimetidine or omeprazole. Also, pharmacodynamics and pharmacokinetics of an oral hormonal contraceptive were not influenced by rotigotine co-administration. Rotigotine was generally well tolerated, with an adverse event profile consistent with dopaminergic stimulation and use of a transdermal patch. These observations, combined with the long-term efficacy demonstrated in clinical studies, support the use of rotigotine as a continuous non-ergot D₃/D₂/D₁ dopamine receptor agonist in the treatment of PD and RLS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Dyskinesia Agents / administration & dosage
  • Anti-Dyskinesia Agents / adverse effects
  • Anti-Dyskinesia Agents / pharmacokinetics*
  • Anti-Dyskinesia Agents / therapeutic use
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / pharmacokinetics
  • Antiparkinson Agents / therapeutic use
  • Comorbidity
  • Dopamine Agonists / administration & dosage
  • Dopamine Agonists / adverse effects
  • Dopamine Agonists / pharmacokinetics*
  • Dopamine Agonists / therapeutic use
  • Drug Interactions
  • Evidence-Based Medicine*
  • Humans
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / epidemiology
  • Parkinson Disease / metabolism
  • Practice Guidelines as Topic
  • Restless Legs Syndrome / drug therapy*
  • Restless Legs Syndrome / epidemiology
  • Restless Legs Syndrome / metabolism
  • Tetrahydronaphthalenes / administration & dosage
  • Tetrahydronaphthalenes / adverse effects
  • Tetrahydronaphthalenes / pharmacokinetics*
  • Tetrahydronaphthalenes / therapeutic use
  • Thiophenes / administration & dosage
  • Thiophenes / adverse effects
  • Thiophenes / pharmacokinetics*
  • Thiophenes / therapeutic use
  • Transdermal Patch* / adverse effects

Substances

  • Anti-Dyskinesia Agents
  • Antiparkinson Agents
  • Dopamine Agonists
  • Tetrahydronaphthalenes
  • Thiophenes
  • rotigotine