Gabapentin enacarbil explained

Gabapentin enacarbil (Horizant, 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 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, the FDA approved Horizant for the treatment of postherpetic neuralgia in adults.[11]

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Notes and References

  1. Landmark CJ, Johannessen SI . Modifications of antiepileptic drugs for improved tolerability and efficacy . Perspectives in Medicinal Chemistry . 2 . 21–39 . 2008 . 19787095 . 2746576 . 10.1177/1177391X0800200001.
  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 . 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 . October 2004 . 15146028 . 10.1124/jpet.104.067934 . 1535942 .
  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 . 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 . October 2004 . 15146029 . 10.1124/jpet.104.067959 . 25152318 .
  4. Cundy KC, Sastry S, Luo W, Zou J, Moors TL, Canafax DM . Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin . Journal of Clinical Pharmacology . 48 . 12 . 1378–88 . December 2008 . 18827074 . 10.1177/0091270008322909 . 23598218 .
  5. Lal R, Sukbuntherng J, Luo W, Huff FJ, Zou J, Cundy KC . 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 . February 2010 . 20137764 . 10.5414/cpp48120.
  6. Merlino G, Serafini A, Lorenzut S, Sommaro M, Gigli GL, Valente M . Gabapentin enacarbil in restless legs syndrome . Drugs of Today . 46 . 1 . 3–11 . January 2010 . 20200691 . 10.1358/dot.2010.46.1.1424766 .
  7. Bogan RK, Bornemann MA, Kushida CA, Trân PV, Barrett RW . Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study . Mayo Clinic Proceedings . 85 . 6 . 512–21 . June 2010 . 20511481 . 10.4065/mcp.2009.0700 . 2878254.
  8. Imamura S, Kushida C . Gabapentin enacarbil (XP13512/GSK1838262) as an alternative treatment to dopaminergic agents for restless legs syndrome . Expert Opinion on Pharmacotherapy . 11 . 11 . 1925–32 . August 2010 . 20629607 . 10.1517/14656566.2010.494598 . 27594934 .
  9. http://www.tradingmarkets.com/news/stock-alert/gsk_glaxosmithkline/xenoport-fda-setback-halts-gabapentin-reformulations-790576.html GlaxoSmithKline/XenoPort: FDA setback halts gabapentin reformulations
  10. Web site: XenoPort, Inc. > Investors > RSS Content. https://archive.today/20120713102633/http://phx.corporate-ir.net/phoenix.zhtml?c=187883&p=RssLanding&cat=news&id=1547555 . dead . 2012-07-13 .
  11. Web site: Jeffrey. Susan. FDA Approves Gabapentin Enacarbil for Postherpetic Neuralgia. Medscape.

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