gabapentin enacarbil

{{Short description|Gabapentin prodrug used to treat restless legs syndrome and shingles complications}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 410508426

| IUPAC_name = (1-{[({(1RS)-1-[isobutyryloxy]ethoxy}carbonyl)
amino]methyl}cyclohexyl)acetic acid

| image = Gabapentin enacarbil.svg

| image_class = skin-invert-image

| width = 235px

| image2 = Gabapentin-enacarbil-3D-balls.png

| image_class2 = bg-transparent

| width2 = 225px

| tradename = Horizant, Regnite

| Drugs.com = {{drugs.com|ppa|gabapentin-enacarbil}}

| DailyMedID = Gabapentin_enacarbil

| licence_US = Horizant

| pregnancy_AU = B1

| pregnancy_US = C

| pregnancy_category =

| legal_UK =

| legal_US = Rx-only

| legal_status =

| routes_of_administration = By mouth

| class = Gabapentinoid

| ATC_prefix = None

| ATC_suffix =

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion = Kidney

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 478296-72-9

| PubChem = 9883933

| IUPHAR_ligand = 7560

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 8059607

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = 75OCL1SPBQ

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 68840

| synonyms = XP-13512

| C=16 | H=27 | N=1 | O=6

| SMILES = CC(C)C(=O)OC(C)OC(=O)NCC1(CCCCC1)CC(=O)O

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C16H27NO6/c1-11(2)14(20)22-12(3)23-15(21)17-10-16(9-13(18)19)7-5-4-6-8-16/h11-12H,4-10H2,1-3H3,(H,17,21)(H,18,19)

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = TZDUHAJSIBHXDL-UHFFFAOYSA-N

}}

Gabapentin enacarbil (Horizant ({{abbr|ER|extended-release}}) ({{abbrlink|U.S.|United States}}), Regnite (in Japan)) is an anticonvulsant and analgesic drug of the gabapentinoid class, and a prodrug to gabapentin.{{cite journal |vauthors=Landmark CJ, Johannessen SI |title=Modifications of antiepileptic drugs for improved tolerability and efficacy |journal=Perspectives in Medicinal Chemistry |volume=2 |pages=21–39 |year=2008 |pmid=19787095 |pmc=2746576 |doi= 10.1177/1177391X0800200001}} It was designed for increased oral bioavailability over gabapentin,{{cite journal |vauthors=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 |title=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 |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=311 |issue=1 |pages=315–23 |date=October 2004 |pmid=15146028 |doi=10.1124/jpet.104.067934 |s2cid=1535942 }}{{cite journal |vauthors=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 |title=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 |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=311 |issue=1 |pages=324–33 |date=October 2004 |pmid=15146029 |doi=10.1124/jpet.104.067959 |s2cid=25152318 }} and human trials showed it to produce extended release of gabapentin with almost twice the overall bioavailability,{{cite journal |vauthors=Cundy KC, Sastry S, Luo W, Zou J, Moors TL, Canafax DM |title=Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin |journal=Journal of Clinical Pharmacology |volume=48 |issue=12 |pages=1378–88 |date=December 2008 |pmid=18827074 |doi=10.1177/0091270008322909 |s2cid=23598218 }} especially when taken with a fatty meal.{{cite journal |vauthors=Lal R, Sukbuntherng J, Luo W, Huff FJ, Zou J, Cundy KC |title=The effect of food with varying fat content on the clinical pharmacokinetics of gabapentin after oral administration of gabapentin enacarbil |journal=International Journal of Clinical Pharmacology and Therapeutics |volume=48 |issue=2 |pages=120–8 |date=February 2010 |pmid=20137764 |doi= 10.5414/cpp48120}} 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.{{cite journal |vauthors=Merlino G, Serafini A, Lorenzut S, Sommaro M, Gigli GL, Valente M |title=Gabapentin enacarbil in restless legs syndrome |journal=Drugs of Today |volume=46 |issue=1 |pages=3–11 |date=January 2010 |pmid=20200691 |doi=10.1358/dot.2010.46.1.1424766 }}{{cite journal |vauthors=Bogan RK, Bornemann MA, Kushida CA, Trân PV, Barrett RW |title=Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study |journal=Mayo Clinic Proceedings |volume=85 |issue=6 |pages=512–21 |date=June 2010 |pmid=20511481 |doi=10.4065/mcp.2009.0700 |pmc=2878254}}{{cite journal |vauthors=Imamura S, Kushida C |title=Gabapentin enacarbil (XP13512/GSK1838262) as an alternative treatment to dopaminergic agents for restless legs syndrome |journal=Expert Opinion on Pharmacotherapy |volume=11 |issue=11 |pages=1925–32 |date=August 2010 |pmid=20629607 |doi=10.1517/14656566.2010.494598 |s2cid=27594934 }}

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.[http://www.tradingmarkets.com/news/stock-alert/gsk_glaxosmithkline/xenoport-fda-setback-halts-gabapentin-reformulations-790576.html GlaxoSmithKline/XenoPort: FDA setback halts gabapentin reformulations]{{Dead link|date=December 2019 |bot=InternetArchiveBot |fix-attempted=yes }} On April 6, 2011, Xenoport received FDA approval for Horizant (gabapentin enacarbil) for the treatment of moderate-to-severe restless legs syndrome.{{Cite web | url=http://phx.corporate-ir.net/phoenix.zhtml?c=187883&p=RssLanding&cat=news&id=1547555 | archive-url=https://archive.today/20120713102633/http://phx.corporate-ir.net/phoenix.zhtml?c=187883&p=RssLanding&cat=news&id=1547555 | url-status=dead | archive-date=2012-07-13 |title = XenoPort, Inc. > Investors > RSS Content}} On June 7, 2012, the FDA approved Horizant for the treatment of postherpetic neuralgia in adults.{{cite web|last1=Jeffrey|first1=Susan|title=FDA Approves Gabapentin Enacarbil for Postherpetic Neuralgia|url=http://www.medscape.com/viewarticle/765233|publisher=Medscape}}