Efficacy of gabapentin enacarbil vs placebo in patients with postherpetic neuralgia and a pharmacokinetic comparison with oral gabapentin

Pain Med. 2011 Jul;12(7):1098-108. doi: 10.1111/j.1526-4637.2011.01139.x. Epub 2011 May 31.


Background: The efficacy of gabapentin in some patients with postherpetic neuralgia (PHN) may be limited by suboptimal drug exposure from unpredictable and saturable absorption. Gabapentin enacarbil (GEn) was designed for absorption by high-capacity transporters expressed throughout the intestine and undergoes rapid postabsorption hydrolysis to gabapentin. GEn extended-release tablets provide sustained, dose-proportional gabapentin exposure. This study assessed the efficacy of GEn vs placebo and compared the pharmacokinetics of gabapentin after oral dosing of GEn or gabapentin in patients with PHN.

Methods: In this double-blind, randomized study, 115 patients with PHN completed a 7-day baseline period and 11-day gabapentin run-in period. Eligible patients were randomized and 101 received double-blind GEn 1,200 mg (624 mg-equivalents gabapentin) (n = 47) or placebo (n = 54), twice daily for 14 days. We evaluated patient-reported pain, sleep, mood, global improvement, and adverse events, plus gabapentin pharmacokinetics.

Results: The improvement in mean weekly pain scores from baseline to the end of treatment (primary endpoint) was significantly greater for GEn (-2.1) vs placebo (-1.2), P = 0.0321. Significant improvements from GEn vs placebo were also seen in sleep, mood, and patient global assessment (P < 0.05). With a 31% lower daily dose of gabapentin equivalents, GEn tablets provided a significant increase in average steady state gabapentin concentrations vs gabapentin capsules in the same patients (n = 42; P = 0.0050).

Conclusions: GEn was effective in providing PHN pain relief, improved gabapentin exposure compared with gabapentin capsules, and was generally safe and well tolerated in patients with PHN.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amines / administration & dosage
  • Amines / therapeutic use*
  • Analgesics / therapeutic use*
  • Carbamates / therapeutic use*
  • Cyclohexanecarboxylic Acids / administration & dosage
  • Cyclohexanecarboxylic Acids / therapeutic use*
  • Double-Blind Method
  • Female
  • Gabapentin
  • Humans
  • Male
  • Middle Aged
  • Neuralgia, Postherpetic / drug therapy*
  • Placebos / therapeutic use*
  • Treatment Outcome*
  • Young Adult
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / therapeutic use


  • 1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid
  • Amines
  • Analgesics
  • Carbamates
  • Cyclohexanecarboxylic Acids
  • Placebos
  • gamma-Aminobutyric Acid
  • Gabapentin