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Identification
Namegabapentin enacarbil
Accession NumberDB08872
TypeSmall Molecule
GroupsApproved
Description

Gabapentin enacarbil is marketed under the name Horizant®. It is a prodrug of gabapentin, and indicated in adults for the treatment of Restless Legs Syndrome (RLS) and postherpetic neuralgia (PHN).

Structure
Thumb
Synonyms
Gabapentina enacarbilo
Gabapentine enacarbil
Gabapentinum enacarbilum
Horizant
XP 13512
XP-13512
XP13512
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Horizanttablet, extended release600 mg/1oralXeno Port Inc.2013-05-01Not applicableUs
Horizanttablet, extended release300 mg/1oralXeno Port Inc.2013-05-01Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNII75OCL1SPBQ
CAS number478296-72-9
WeightNot Available
Chemical FormulaNot Available
InChI KeyNot Available
InChINot Available
IUPAC NameNot Available
SMILESNot Available
Taxonomy
ClassificationNot classified
Pharmacology
IndicationFor the treatment of adult Restless Legs Syndrome (RLS) and postherpetic neuralgia (PHN).
PharmacodynamicsSince gabapentin enacarbil is a prodrug of gabapentin, it's physiological effects are the same as gabapentin. Concerning PHN, gabapentin prevents allodynia and hyperalgesia.
Mechanism of actionAlthough the exact mechanism of action of gabapentin in RLS and PHN is unknown, it is presumed to involve the descending noradrenergic system, resulting in the activation of spinal alpha2-adrenergic receptors.
Related Articles
AbsorptionGabapentin enacarbil is absorbed in the intestines by active transport through the proton-linked monocarboxylate transporter, MCT-1.
Volume of distribution

The volume of distribution is 76L.

Protein bindingGabapentin plasma protein binding is less than 3%.
Metabolism

Gabapentin enacarbil does not interact with any of the major cytochrome P450 enzymes.

Route of eliminationGabapentin enacarbil is eliminated primarily in the urine (94%) and to a lesser extent in the feces (5%).
Half lifeThe elimination half-life of gabapentin is 5.1 to 6.0 hours.
Clearance

Renal clearance of gabapentin is 5 to 7 L/hr.

ToxicityMost common adverse reactions are headache, dizziness, and somnolence.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, extended releaseoral300 mg/1
Tablet, extended releaseoral600 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6818787 No2002-11-062022-11-06Us
US8026279 No2006-11-102026-11-10Us
US8048917 No2002-11-062022-11-06Us
US8114909 No2006-04-112026-04-11Us
US8686034 No2005-01-242025-01-24Us
US8795725 No2009-06-102029-06-10Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting pointMelting onset of about 64°C.From FDA label.
water solubilitySolubility of 0.5 mg/mL in water From FDA label.
pKapKa 5.0From The Merck Index.
Predicted PropertiesNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
References
Synthesis Reference

1. 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. J Pharmacol Exp Ther. 2004 Oct;311(1):315-23. Epub 2004 May 14.

General References
  1. 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. J Pharmacol Exp Ther. 2004 Oct;311(1):324-33. Epub 2004 May 14. [PubMed:15146029 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (347 KB)
MSDSDownload (30.7 KB)
Interactions
Drug Interactions
Drug
Azelastinegabapentin enacarbil may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with gabapentin enacarbil.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of gabapentin enacarbil.
Buprenorphinegabapentin enacarbil may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of gabapentin enacarbil.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of gabapentin enacarbil.
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of gabapentin enacarbil.
EthanolEthanol may increase the central nervous system depressant (CNS depressant) activities of gabapentin enacarbil.
Hydrocodonegabapentin enacarbil may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of gabapentin enacarbil.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with gabapentin enacarbil.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of gabapentin enacarbil.
Methotrimeprazinegabapentin enacarbil may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
Metyrosinegabapentin enacarbil may increase the sedative activities of Metyrosine.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of gabapentin enacarbil.
Mirtazapinegabapentin enacarbil may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of gabapentin enacarbil.
Orphenadrinegabapentin enacarbil may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
Paraldehydegabapentin enacarbil may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParoxetineThe risk or severity of adverse effects can be increased when gabapentin enacarbil is combined with Paroxetine.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of gabapentin enacarbil.
Pramipexolegabapentin enacarbil may increase the sedative activities of Pramipexole.
Ropinirolegabapentin enacarbil may increase the sedative activities of Ropinirole.
Rotigotinegabapentin enacarbil may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with gabapentin enacarbil.
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of gabapentin enacarbil.
Suvorexantgabapentin enacarbil may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of gabapentin enacarbil.
Thalidomidegabapentin enacarbil may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
Zolpidemgabapentin enacarbil may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Food Interactions
  • No food effects.

Transporters

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Symporter activity
Specific Function:
Acts as an electrogenic sodium (Na(+)) and chloride (Cl-)-dependent sodium-coupled solute transporter, including transport of monocarboxylates (short-chain fatty acids including L-lactate, D-lactate, pyruvate, acetate, propionate, valerate and butyrate), lactate, mocarboxylate drugs (nicotinate, benzoate, salicylate and 5-aminosalicylate) and ketone bodies (beta-D-hydroxybutyrate, acetoacetate ...
Gene Name:
SLC5A8
Uniprot ID:
Q8N695
Molecular Weight:
66577.005 Da
References
  1. 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. J Pharmacol Exp Ther. 2004 Oct;311(1):315-23. Epub 2004 May 14. [PubMed:15146028 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Sodium-dependent multivitamin transmembrane transporter activity
Specific Function:
Transports pantothenate, biotin and lipoate in the presence of sodium.
Gene Name:
SLC5A6
Uniprot ID:
Q9Y289
Molecular Weight:
68641.27 Da
References
  1. 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. J Pharmacol Exp Ther. 2004 Oct;311(1):315-23. Epub 2004 May 14. [PubMed:15146028 ]
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Drug created on May 02, 2013 15:20 / Updated on May 30, 2016 02:08