Gabapentin enacarbil: Difference between revisions

| IUPAC_name = 1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid

| image = XP-13512_structure.png

| CAS_number = 478296-72-9

| ATC_prefix =

| ATC_suffix =

| PubChem = 9883933

| DrugBank =

| ChemSpiderID =

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

| molecular_weight = 329.389 g/mol

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

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion = [[Kidney|Renal]]

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category =

| legal_status =

| legal_UK =

| routes_of_administration = Oral

'''Gabapentin enacarbil''' ('''Horizant''', '''XP-13512''') is a [[prodrug]] for the [[anticonvulsant]] and [[analgesic]] drug [[gabapentin]].<ref name="pmid19787095">{{cite journal |author=Landmark CJ, Johannessen SI |title=Modifications of antiepileptic drugs for improved tolerability and efficacy |journal=Perspectives in Medicinal Chemistry |volume=2 |issue= |pages=21–39 |year=2008 |pmid=19787095 |pmc=2746576 |doi= |url=}}</ref> It was designed for increased oral [[bioavailability]] over gabapentin,<ref name="pmid15146028">{{cite journal |author=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 |year=2004 |month=October |pmid=15146028 |doi=10.1124/jpet.104.067934 |url=}}</ref><ref name="pmid15146029">{{cite journal |author=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 |year=2004 |month=October |pmid=15146029 |doi=10.1124/jpet.104.067959 |url=}}</ref> and human trials showed it to produce extended release of gabapentin with almost twice the overall bioavailability,<ref name="pmid18827074">{{cite journal |author=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 |year=2008 |month=December |pmid=18827074 |doi=10.1177/0091270008322909 |url=}}</ref> especially when taken with a fatty meal.<ref name="pmid20137764">{{cite journal |author=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 |year=2010 |month=February |pmid=20137764 |doi= |url=}}</ref> Gabapentin enacarbil has passed human [[clinical trial]]s for the treatment of [[restless legs syndrome]], and initial results have shown it to be well tolerated and reasonably effective.<ref name="pmid20200691">{{cite journal |author=Merlino G, Serafini A, Lorenzut S, Sommaro M, Gigli GL, Valente M |title=Gabapentin enacarbil in restless legs syndrome |journal=Drugs of Today (Barcelona, Spain : 1998) |volume=46 |issue=1 |pages=3–11 |year=2010 |month=January |pmid=20200691 |doi=10.1358/dot.2010.46.1.1424766 |url=}}</ref><ref name="pmid20511481">{{cite journal |author=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. Mayo Clinic |volume=85 |issue=6 |pages=512–21 |year=2010 |month=June |pmid=20511481 |doi=10.4065/mcp.2009.0700 |url=}}</ref><ref name="pmid20629607">{{cite journal |author=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 |year=2010 |month=August |pmid=20629607 |doi=10.1517/14656566.2010.494598 |url=}}</ref>

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.<ref>[http://www.tradingmarkets.com/news/stock-alert/gsk_glaxosmithkline/xenoport-fda-setback-halts-gabapentin-reformulations-790576.html GlaxoSmithKline/XenoPort: FDA setback halts gabapentin reformulations]</ref>

{{Analgesics}}