Gabapentin enacarbil, a gabapentin prodrug for the treatment of the neurological symptoms associated with disorders such as restless legs syndrome

Restless Legs Syndrome (RLS) is a sleep-related movement disorder characterized by an urge to move the legs accompanied by unpleasant symptoms. Dopaminergic agents currently represent the first-line therapy for RLS. However, some patients are unable to continue with this pharmacological approach in the long term because of 'augmentation' or other adverse events. Limited studies with the anticonvulsant/analgesic agent gabapentin have demonstrated that this drug might be useful in the treatment of primary and uremic RLS. Unfortunately, gabapentin has an unfavorable pharmacokinetic profile characterized by a dose-dependent bioavailability. Gabapentin enacarbil, a prodrug of gabapentin, is currently being developed by XenoPort Inc/Astellas Pharma Inc/GlaxoSmithKline plc in order to overcome this limitation. In vitro and in vivo studies have demonstrated that gabapentin enacarbil provides a dose-proportional exposure to gabapentin when orally administered. Gabapentin enacarbil has proved to be beneficial in treating RLS symptoms in several phase II and III clinical trials. In addition, these trials have demonstrated that gabapentin enacarbil is safe and well tolerated, causing transient and mild or moderate adverse events. Gabapentin enacarbil is an interesting compound, which is potentially useful in treating RLS patients who report severe adverse events under dopaminergic agents. The author concludes that additional studies are required in order to better assess the efficacy and safety of gabapentin enacarbil on RLS.