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.

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    • "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]. "
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    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.
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    • "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. "
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    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.
    11/2010; 2:45-55. DOI:10.4137/JCNSD.S4886
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    ABSTRACT: Hyperexcitation in the central nervous system is the root cause of a number of disorders of the brain ranging from acute injury to chronic and progressive diseases. The major limitation to treatment of these ailments is the miniscule, yet formidable blood-brain barrier. To deliver therapeutic agents to the site of desired action, a number of biomedical engineering strategies have been developed including prodrug formulations that allow for either passive diffusion or active transport across this barrier. In the case of prodrugs, once in the brain compartment, the active therapeutic agent is released. In this review, we discuss in some detail a number of factors related to treatment of central nervous system hyperexcitation including molecular targets, disorders, prodrug strategies, and focused case studies of a number of therapeutics that are at a variety of stages of clinical development.
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