Pharmacokinetics and tolerability of single escalating doses of gabapentin enacarbil: A randomized-sequence, double-blind, placebo-controlled crossover study in healthy volunteers

Lal, Ritu; Sukbuntherng, Juthamas; Luo, Wendy; Chen, Dan; Vu, Amanda; Tovera, James; Cundy, Kenneth C.

doi:10.1016/j.clinthera.2009.07.026

Cited by 46 publications

(40 citation statements)

References 20 publications

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“…Weight was then reduced in the taper period, although it persisted in the placebo group. Dizziness and nausea were reported at higher rates than placebo in a further tolerability study, with somnolence additionally appearing, amongst other symptoms, at doses greater than 3,600 mg, which is above the licensed dose for GpIR in the United Kingdom 24. Other data taken from controlled trials in patients diagnosed with RLS reported that 20% of patients suffered somnolence or sedation at 600 mg compared to 6% in patients taking placebo, with symptoms persisting past treatment in 30% 17.…”

Section: Safety and Tolerability Issuesmentioning

confidence: 84%

“…B = randomized, double-blind, placebo controlled trial assessing efficacy and safety in patients with PHN 20. C = randomized, double-blind, placebo controlled, cross over study in healthy volunteers 24–. indicates data unavailable.…”

Section: Tablementioning

confidence: 99%

“…J Pain . 2013; l4(6):590–603;20 and data taken with permission from Clinical Therapy , 31, Lal R, Sukbuntherng J, Luo W, et al, 1776–1786, copyright Elsevier (2009) 24

Abbreviations: CNS, central nervous system; GI, gastrointestinal; PHN, postherpetic neuralgia; n, number of patients; RLS, restless leg syndrome.

…”

Section: Tablementioning

confidence: 99%

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Gabapentin enacarbil extended release for the treatment of postherpetic neuralgia in adults

Thomas

Farquhar-Smith

2013

TCRM

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The development of biomedical technology is allowing refinement of drug therapies in order to improve medication profiles and benefit patients. Gabapentin (Gp) is a medication licensed globally for various indications, including postherpetic neuralgia. It has a pharmacokinetic profile which has been suggested may limit its clinical effects and reduce medication compliance. In 2012, the US Food and Drug Administration licensed a novel preparation which aims to circumvent these limitations. Gp enacarbil is a prodrug of Gp, which is additionally prepared in an extended release preparation. The resulting compound has an improved absorption profile and a reduced dosing frequency in comparison to immediate release Gp. An absence of comparative data, however, limits the direct evaluation of the medication to both immediate release and other extended release preparations available on the market. Additionally, no data are currently available addressing efficacy, tolerability, or side effects with other first line treatments of postherpetic neuralgia. Additional experimental data should be sought to clarify the position of Gp enacarbil, both within postherpetic neuralgia treatment protocols and in relation to the increasing numbers of gabapentinoids available.

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Section: Safety and Tolerability Issuesmentioning

confidence: 84%

Section: Tablementioning

confidence: 99%

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Gabapentin enacarbil extended release for the treatment of postherpetic neuralgia in adults

Thomas

Farquhar-Smith

2013

TCRM

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“…17 GEn delivers predictable and sustained gabapentin exposure (bioavailability ≥ 68% based on urinary recovery of gabapentin in healthy adults) compared with mgequivalent doses of gabapentin. 16,18,19 In a 12-week, placebo-controlled study, subjects with moderate-to-severe primary RLS reported significantly improved RLS symptoms with GEn 1200 mg compared with placebo. 20 A shorter 2-week study demonstrated significant treatment benefit in subjects with primary RLS with GEn 1200 mg compared with placebo, but not with GEn 600 mg. 21 The present study evaluated the efficacy and tolerability of GEn 1200 mg and 600 mg compared with placebo in subjects with moderate-tosevere primary RLS, to confirm the previous findings for GEn 1200 mg and to further evaluate whether 12-week exposure to GEn 600 mg provided significant treatment benefits.…”

Section: Efficacy Assessmentsmentioning

confidence: 99%

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Tolerability of Gabapentin Enacarbil in Subjects with Restless Legs Syndrome

Lee

Ziman²,

Perkins³

et al. 2011

Journal of Clinical Sleep Medicine

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“…Levels of the intact prodrug were low and transient. Gabapentin enacarbil XR provided dose-proportional exposure of gabapentin over the dose range 24006000 mg (12503125 mg equivalent gabapentin) [Lal et al 2009]. …”

Section: Phase I Trialsmentioning

confidence: 99%

The use of gabapentin enacarbil in the treatment of restless legs syndrome

Yaltho

Ondo

2010

Ther Adv Neurol Disord

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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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Pharmacokinetics and tolerability of single escalating doses of gabapentin enacarbil: A randomized-sequence, double-blind, placebo-controlled crossover study in healthy volunteers

Cited by 46 publications

References 20 publications

Gabapentin enacarbil extended release for the treatment of postherpetic neuralgia in adults

Gabapentin enacarbil extended release for the treatment of postherpetic neuralgia in adults

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Tolerability of Gabapentin Enacarbil in Subjects with Restless Legs Syndrome

The use of gabapentin enacarbil in the treatment of restless legs syndrome

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