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.
Merlino
Giovanni
G
Sleep Disorder Center, Santa Maria della Misericordia University Hospital, Piazzale S Maria della Misericordia, Udine, Italy.
Serafini
Anna
A
Young
Jeong Jin
JJ
Robiony
Francesca
F
Gigli
Gian Luigi
GL
Valente
Mariarosaria
M
D000818:Animals; D002219:Carbamates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D011355:Prodrugs; D012148:Restless Legs Syndrome / Q000188:drug therapy*; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
C493250:1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid; D002219:Carbamates; D011355:Prodrugs; D005680:gamma-Aminobutyric Acid