Gabapentin enacarbil XR is a new extended-release formulation which attempts to 
overcome the reduced efficacy of shorter-acting gabapentin, with sustained 
delivery over a 24-hour period. It is a gabapentin prodrug which is efficiently 
and rapidly converted to gabapentin during active transport throughout the 
length of the intestine via high-capacity monocarboxylate type 1 nutrient 
transporters unlike its predecessor, which is absorbed via low-capacity 
transporters largely confined to the upper intestinal region. Its lack of 
saturable absorption allows for dose-proportional absorption and hence increased 
bioavailability. Several clinical trials addressing its efficacy in moderate to 
severe restless legs syndrome (RLS) demonstrate improvements in the 
International RLS Rating Scale after a 2-week to 3-month period. Open-label 
studies of 52 weeks' duration showed maintenance of symptom reduction with 
once-daily administration of the extended-release formulation. The most commonly 
reported treatment-emergent adverse effects were somnolence and dizziness. 
Although the incidence of emergent adverse effects is high, it is comparable 
with that of gabapentin. No studies thus far have documented augmentation as an 
issue, unlike that observed with most dopaminergic agents. In addition, both 
dopamine precursors and agonists have not been shown to increase slow wave sleep 
or improve overall sleep architecture consistently despite improvement in the 
periodic leg movement index, in contrast with gabapentin enacarbil. Presently, 
gabapentin enacarbil has not been approved by the Therapeutic Goods 
Administration or Medsafe for use in RLS. The cost of this medication may also 
be a potential barrier for many patients. Future comparative efficacy studies 
with gabapentin, first-line dopaminergic agents, rotigotine, being the other 
once daily RLS medication, and pregabalin, the structural analog of gabapentin, 
will be necessary.