ADMET considerations for restless leg syndrome drug treatments

Expert Opin Drug Metab Toxicol. 2012 Oct;8(10):1247-61. doi: 10.1517/17425255.2012.708023. Epub 2012 Jul 18.

Abstract

Introduction: Restless legs syndrome (RLS) is a common neurological disorder that might impair nocturnal rest causing decreased alertness, depressed mood, reduced job performance, and poor quality of life. In patients affected by severe RLS, a pharmacological treatment is mandatory.

Areas covered: The present review is based on a search using PubMed from 1994 to 2012. It is focused on the Absorption, Distribution, Metabolism, Elimination and Toxicology (ADMET) characteristics of the most used medications for RLS. In particular, the ADMET characteristics of dopaminergic agents, anticonvulsants able to improve neuropathic pain, and iron were discussed.

Expert opinion: Clinical trials have showed that non-ergolic dopamine agonists are efficacious and safe for patients affected by moderate to severe idiopathic RLS. However, no head-to-head study has compared the long-term effects of the three dopamine agonists approved by the FDA for RLS (ropinirole, pramipexole, and rotigotine). Moreover, further studies should investigate the extended-release formulation of ropinirole and pramipexole in RLS patients affected by all day long distressing symptoms. A standardized treatment for symptomatic forms of RLS is lacking. Randomized, placebo-controlled trials should be performed at least in RLS patients with peripheral neuropathic and chronic kidney disease. Concerning RLS due to iron deficiency, a head-to-head study comparing efficacy, safety and compliance of oral iron versus intravenous one seems to be needed.

Publication types

  • Review

MeSH terms

  • Amines / adverse effects
  • Amines / pharmacokinetics
  • Amines / therapeutic use
  • Anticonvulsants / adverse effects
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / therapeutic use
  • Benzothiazoles / adverse effects
  • Benzothiazoles / pharmacokinetics
  • Benzothiazoles / therapeutic use*
  • Carbamates / adverse effects
  • Carbamates / pharmacokinetics
  • Carbamates / therapeutic use
  • Cyclohexanecarboxylic Acids / adverse effects
  • Cyclohexanecarboxylic Acids / pharmacokinetics
  • Cyclohexanecarboxylic Acids / therapeutic use
  • Dopamine Agents / adverse effects
  • Dopamine Agents / pharmacokinetics
  • Dopamine Agents / therapeutic use*
  • Dopamine Agonists / adverse effects
  • Dopamine Agonists / pharmacokinetics
  • Dopamine Agonists / therapeutic use
  • Ergolines / adverse effects
  • Ergolines / pharmacokinetics
  • Ergolines / therapeutic use
  • Gabapentin
  • Humans
  • Indoles / adverse effects
  • Indoles / pharmacokinetics
  • Indoles / therapeutic use*
  • Levodopa / adverse effects
  • Levodopa / pharmacokinetics
  • Levodopa / therapeutic use
  • Neuralgia / drug therapy
  • Neuralgia / physiopathology
  • Pramipexole
  • Pregabalin
  • Randomized Controlled Trials as Topic
  • Restless Legs Syndrome / drug therapy*
  • Tetrahydronaphthalenes / adverse effects
  • Tetrahydronaphthalenes / pharmacokinetics
  • Tetrahydronaphthalenes / therapeutic use*
  • Thiophenes / adverse effects
  • Thiophenes / pharmacokinetics
  • Thiophenes / therapeutic use*
  • Treatment Outcome
  • gamma-Aminobutyric Acid / adverse effects
  • gamma-Aminobutyric Acid / analogs & derivatives
  • gamma-Aminobutyric Acid / pharmacokinetics
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • 1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid
  • Amines
  • Anticonvulsants
  • Benzothiazoles
  • Carbamates
  • Cyclohexanecarboxylic Acids
  • Dopamine Agents
  • Dopamine Agonists
  • Ergolines
  • Indoles
  • Tetrahydronaphthalenes
  • Thiophenes
  • ropinirole
  • Levodopa
  • Pregabalin
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Pramipexole
  • rotigotine