Gabapentin enacarbil

Gabapentin enacarbil (Horizant (IR) (U.S.), Regnite (in Japan)) is an anticonvulsant and analgesic drug of the gabapentinoid class, and a prodrug to gabapentin.[1] It was designed for increased oral bioavailability over gabapentin,[2][3] and human trials showed it to produce extended release of gabapentin with almost twice the overall bioavailability,[4] especially when taken with a fatty meal.[5] Gabapentin enacarbil has passed human clinical trials for the treatment of restless legs syndrome, and initial results have shown it to be well tolerated and reasonably effective.[6][7][8]

Gabapentin enacarbil
Clinical data
Trade namesHorizant, Regnite
Other namesXP-13512
License data
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    administration    		By mouth
    Drug classGabapentinoid
    Legal status
    Legal status
    Pharmacokinetic data
    ExcretionRenal
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    ChemSpider
    UNII
    ChEBI
    Chemical and physical data
    FormulaC16H27NO6
    Molar mass329.389 g/mol g·mol−1
    3D model (JSmol)
     NY (what is this?)  (verify)

    Gabapentin enacarbil was denied approval by the U.S. Food and Drug Administration (FDA) in February 2010, citing concerns about possible increased cancer risk shown by some animal studies. Similar concerns had been raised about gabapentin itself in the past, but were felt to be outweighed by its clinical utility as an anticonvulsant, whereas the treatment of restless legs syndrome was not seen to justify the same kind of risk.[9] On April 6, 2011, Xenoport received FDA approval for Horizant (gabapentin enacarbil) for the treatment of moderate-to-severe restless legs syndrome.[10] On June 7, 2012, FDA approved Horizant for the treatment of postherpetic neuralgia in adults.[11]

    References
    1. Landmark CJ, Johannessen SI (2008). "Modifications of antiepileptic drugs for improved tolerability and efficacy". Perspectives in Medicinal Chemistry. 2: 21–39. PMC 2746576. PMID 19787095.
    2. Cundy KC, Branch R, Chernov-Rogan T, Dias T, Estrada T, Hold K, Koller K, Liu X, Mann A, Panuwat M, Raillard SP, Upadhyay S, Wu QQ, Xiang JN, Yan H, Zerangue N, Zhou CX, Barrett RW, Gallop MA (October 2004). "XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: I. Design, synthesis, enzymatic conversion to gabapentin, and transport by intestinal solute transporters". The Journal of Pharmacology and Experimental Therapeutics. 311 (1): 315–23. doi:10.1124/jpet.104.067934. PMID 15146028.
    3. Cundy KC, Annamalai T, Bu L, De Vera J, Estrela J, Luo W, Shirsat P, Torneros A, Yao F, Zou J, Barrett RW, Gallop MA (October 2004). "XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: II. Improved oral bioavailability, dose proportionality, and colonic absorption compared with gabapentin in rats and monkeys". The Journal of Pharmacology and Experimental Therapeutics. 311 (1): 324–33. doi:10.1124/jpet.104.067959. PMID 15146029.
    4. Cundy KC, Sastry S, Luo W, Zou J, Moors TL, Canafax DM (December 2008). "Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin". Journal of Clinical Pharmacology. 48 (12): 1378–88. doi:10.1177/0091270008322909. PMID 18827074.
    5. Lal R, Sukbuntherng J, Luo W, Huff FJ, Zou J, Cundy KC (February 2010). "The effect of food with varying fat content on the clinical pharmacokinetics of gabapentin after oral administration of gabapentin enacarbil". International Journal of Clinical Pharmacology and Therapeutics. 48 (2): 120–8. doi:10.5414/cpp48120. PMID 20137764.
    6. Merlino G, Serafini A, Lorenzut S, Sommaro M, Gigli GL, Valente M (January 2010). "Gabapentin enacarbil in restless legs syndrome". Drugs of Today (Barcelona, Spain : 1998). 46 (1): 3–11. doi:10.1358/dot.2010.46.1.1424766. PMID 20200691.
    7. Bogan RK, Bornemann MA, Kushida CA, Trân PV, Barrett RW (June 2010). "Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study". Mayo Clinic Proceedings. 85 (6): 512–21. doi:10.4065/mcp.2009.0700. PMC 2878254. PMID 20511481.
    8. Imamura S, Kushida C (August 2010). "Gabapentin enacarbil (XP13512/GSK1838262) as an alternative treatment to dopaminergic agents for restless legs syndrome". Expert Opinion on Pharmacotherapy. 11 (11): 1925–32. doi:10.1517/14656566.2010.494598. PMID 20629607.
    9. GlaxoSmithKline/XenoPort: FDA setback halts gabapentin reformulations
    11. Jeffrey, Susan. "FDA Approves Gabapentin Enacarbil for Postherpetic Neuralgia". Medscape.


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