The use of gabapentin enacarbil in the treatment of restless legs syndrome

Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
Therapeutic Advances in Neurological Disorders (Impact Factor: 3.14). 09/2010; 3(5):269-75. DOI: 10.1177/1756285610378059
Source: PubMed


Restless legs syndrome (RLS) is a common sleep-related neurological disorder that is characterized by the urge to move, worsening at rest, improvement with activity, and worsening in the evening and night. Dopamine agonists are usually the first-line therapy. Other agents including benzodiazepines, narcotics, and anticonvulsants have been used to treat RLS. Gabapentin has been shown to improve RLS in a small number of clinical studies, but is limited by its short half-life and variable bioavailability. Gabapentin enacarbil is a novel prodrug of gabapentin designed to overcome these pharmacokinetic limitations. In vitro and in vivo studies have demonstrated that gabapentin enacarbil has improved absorption, bioavailability and pharmacokinetics compared with gabapentin. Phase II and III studies have demonstrated that gabapentin enacarbil is generally well tolerated and is useful in the treatment of RLS.

Download full-text


Available from: William G Ondo
  • Source
    • "Idiopathic RLS is generally treated with DA; however within the context of PD patients who are already on DA, treatment with agents such as gabapentin enacarbil or opiates has also been used [144]. It should be noted that caffeine, alcohol, central acting antihistamines, dopamine antagonists, tricyclic antidepressants and serotoninergic reuptake inhibitors can exacerbate RLS [145]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Academic Editor: Birgit Frauscher Copyright © 2012 Todd J. Swick. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Parkinson's disease (PD) has traditionally been characterized by its cardinal motor symptoms of bradykinesia, rigidity, resting tremor, and postural instability. However, PD is increasingly being recognized as a multidimensional disease associated with myriad nonmotor symptoms including autonomic dysfunction, mood disorders, cognitive impairment, pain, gastrointestinal disturbance, impaired olfaction, psychosis, and sleep disorders. Sleep disturbances, which include sleep fragmentation, daytime somnolence, sleep-disordered breathing, restless legs syndrome (RLS), nightmares, and rapid eye movement (REM) sleep behavior disorder (RBD), are estimated to occur in 60% to 98% of patients with PD. For years nonmotor symptoms received little attention from clinicians and researchers, but now these symptoms are known to be significant predictors of morbidity in determining quality of life, costs of disease, and rates of institutionalization. A discussion of the clinical aspects, pathophysiology, evaluation techniques, and treatment options for the sleep disorders that are encountered with PD is presented.
    Full-text · Article · Dec 2012 · Parkinson's Disease
  • Source
    • "Drug bioavailability is reduced and continues to lessen as doses are increased. GBP is quickly excreted unaltered by the kidneys within the urine possessing a half-life ranging between five and seven hours.1 A limited half-life alongside an unpredictable bioavailability restricts use.3 Regular dosing is thus required to maintain beneficial concentrations. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Restless Legs Syndrome (RLS) is a prevalent sleep-associated movement disorder greatly affecting patients' quality of life (QoL). Several drugs can be used to control this condition although the first-line dopamine agents often cause adverse effects. Non-dopaminergic drugs such as oral gabapentin (GBP) have been more recently advocated. Despite ameliorating RLS symptoms, GBP's pharmacokinetic limitations restrict its overall effectiveness. A novel specifically designed prodrug, gabapentin enacarbil (GE), has demonstrated successful RLS alleviation with a superior pharmacokinetic profile. This review aims to examine the efficacy and tolerability of both GBP and GE as pharmacotherapy for RLS. Despite some heterogeneity and limitations across research methodologies, GE appears to be a potential RLS therapy superior to GBP and other dopaminergic agents.
    Preview · Article · Nov 2010
  • [Show abstract] [Hide abstract]
    ABSTRACT: Restless legs syndrome (RLS), formally identified and described by Ekbom in the 1940s, is a common clinical disorder, characterized by an overwhelming urge to move the legs, often accompanied by uncomfortable and unpleasant sensations. This impulse can also be present in the upper limbs or other parts of the body. Well recognized in the adult population, the symptoms associated with this condition have commonly been reported to originate in childhood. However, identifying prospectively children suffering from RLS is still a challenging issue. Iron deficiency has been recognized as a feature frequently associated with RLS. Some authors also make a connection with the deficiency, RLS and other common problems encountered in children, such as attention deficit disorder with hyperactivity (ADHD). Linkage to different chromosomal loci has been achieved in recent genetic studies of large kindred, as well as identification of specific genes. Therapeutic considerations in children range from providing sound sleep hygiene to intervening pharmacologically. In that regard, use of iron supplements, dopaminergic stimulation, anticonvulsants, opiates, and benzodiazepines will be assessed along with newer options, such as rotigotine and gabapentin enacarbil. Considerations specific to childhood do apply, as no pharmacological therapy for restless legs syndrome have been approved by the Federal Drug Administration (FDA) in individuals of the pediatric age group.
    No preview · Article · Apr 2011 · Current pharmaceutical design
Show more