Identification
- Summary
Gabapentin enacarbil is a gabapentin prodrug used to treat Restless Legs Syndrome (RLS) and postherpetic neuralgia (PHN).
- Brand Names
- Horizant
- Generic Name
- Gabapentin enacarbil
- DrugBank Accession Number
- DB08872
- Background
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).
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Gabapentin enacarbil (DB08872)
- Weight
- Average: 329.393
Monoisotopic: 329.183837593 - Chemical Formula
- C16H27NO6
- Synonyms
- Gabapentin enacarbil
- Gabapentina enacarbilo
- Gabapentine enacarbil
- Gabapentinum enacarbilum
- External IDs
- ASP-8825
- ASP8825
- GSK-1838262
- GSK1838262
- XP 13512
- XP-13512
- XP13512
Pharmacology
- Indication
For the treatment of adult Restless Legs Syndrome (RLS) and postherpetic neuralgia (PHN).
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Since 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 action
Although 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.
Target Actions Organism UVoltage-dependent calcium channel subunit alpha-2/delta-1 Not Available Humans UVoltage-dependent calcium channel subunit alpha-2/delta-2 Not Available Humans - Absorption
Gabapentin 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 binding
Gabapentin plasma protein binding is less than 3%.
- Metabolism
Gabapentin enacarbil does not interact with any of the major cytochrome P450 enzymes.
- Route of elimination
Gabapentin enacarbil is eliminated primarily in the urine (94%) and to a lesser extent in the feces (5%).
- Half-life
The elimination half-life of gabapentin is 5.1 to 6.0 hours.
- Clearance
Renal clearance of gabapentin is 5 to 7 L/hr.
- Adverse Effects
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Most common adverse reactions are headache, dizziness, and somnolence.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Gabapentin enacarbil is combined with 1,2-Benzodiazepine. Abacavir Abacavir may decrease the excretion rate of Gabapentin enacarbil which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Gabapentin enacarbil which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Gabapentin enacarbil which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Gabapentin enacarbil which could result in a higher serum level. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Gabapentin enacarbil. Acetophenazine The risk or severity of adverse effects can be increased when Acetophenazine is combined with Gabapentin enacarbil. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Gabapentin enacarbil which could result in a higher serum level. Aclidinium Gabapentin enacarbil may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acrivastine Gabapentin enacarbil may decrease the excretion rate of Acrivastine which could result in a higher serum level. 
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- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Active Moieties
Name Kind UNII CAS InChI Key Gabapentin prodrug 6CW7F3G59X 60142-96-3 UGJMXCAKCUNAIE-UHFFFAOYSA-N - Product Images
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Horizant Tablet, extended release 300 mg/1 Oral Glaxosmithkline Inc 2011-12-15 2014-12-05 US 
Horizant Tablet, extended release 600 mg/1 Oral Azurity Pharmaceuticals, Inc. (formerly Arbor Pharmaceuticals) 2013-05-01 Not applicable US 
Horizant Tablet, extended release 300 mg/1 Oral Azurity Pharmaceuticals, Inc. (formerly Arbor Pharmaceuticals) 2013-05-01 Not applicable US Horizant Tablet, extended release 600 mg/1 Oral Glaxosmithkline Inc 2011-04-07 2014-07-22 US 
Horizant Tablet, extended release 300 mg/1 Oral XenoPort Inc. 2013-05-01 2013-04-04 US Horizant Tablet, extended release 300 mg/1 Oral REMEDYREPACK INC. 2016-09-02 2017-09-02 US
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Gamma amino acids and derivatives
- Alternative Parents
- Dicarboxylic acids and derivatives / Carbamate esters / Organic carbonic acids and derivatives / Carboxylic acid esters / Carboxylic acids / Acetals / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives show 1 more
- Substituents
- Acetal / Aliphatic homomonocyclic compound / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Carboxylic acid / Carboxylic acid ester / Dicarboxylic acid or derivatives / Gamma amino acid or derivatives / Hydrocarbon derivative show 6 more
- Molecular Framework
- Aliphatic homomonocyclic compounds
- External Descriptors
- carbamate ester, monocarboxylic acid, carboxylic ester, acetal (CHEBI:68840)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 75OCL1SPBQ
- CAS number
- 478296-72-9
- InChI Key
- TZDUHAJSIBHXDL-UHFFFAOYSA-N
- InChI
- InChI=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)
- IUPAC Name
- 2-(1-{[({1-[(2-methylpropanoyl)oxy]ethoxy}carbonyl)amino]methyl}cyclohexyl)acetic acid
- SMILES
- CC(C)C(=O)OC(C)OC(=O)NCC1(CC(O)=O)CCCCC1
References
- Synthesis Reference
- 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
- 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. [Article]
- Bialer M: New antiepileptic drugs that are second generation to existing antiepileptic drugs. Expert Opin Investig Drugs. 2006 Jun;15(6):637-47. [Article]
- 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. [Article]
- External Links
- KEGG Drug
- D09539
- PubChem Compound
- 9883933
- PubChem Substance
- 347827805
- ChemSpider
- 8059607
- 1101333
- ChEBI
- 68840
- ChEMBL
- CHEMBL1628502
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Gabapentin_enacarbil
- FDA label
- Download (347 KB)
- MSDS
- Download (30.7 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Postoperative pain 1 4 Completed Treatment Restless Legs Syndrome (RLS) 3 4 Recruiting Treatment Alzheimer's Disease (AD) / Coronavirus Disease 2019 (COVID‑19) 1 4 Recruiting Treatment Restless Legs Syndrome (RLS) 2 4 Terminated Treatment Restless Legs Syndrome (RLS) 1 4 Unknown Status Treatment Restless Legs Syndrome (RLS) 1 4 Withdrawn Treatment Acute Pain / Facial Pain / Postoperative pain 1 3 Completed Treatment Restless Legs Syndrome (RLS) 6 3 Terminated Supportive Care Head And Neck Cancer / Narcotics Use 1 2 Completed Prevention Migraine 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, extended release Oral 300 mg/1 Tablet, extended release Oral 600 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8048917 No 2011-11-01 2022-11-06 US US8114909 No 2012-02-14 2026-04-11 US US8686034 No 2014-04-01 2025-01-24 US US8795725 No 2014-08-05 2029-06-10 US US8026279 No 2011-09-27 2026-11-10 US US6818787 No 2004-11-16 2022-11-06 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) Melting onset of about 64°C. From FDA label. water solubility Solubility of 0.5 mg/mL in water From FDA label. pKa pKa 5.0 From The Merck Index. - Predicted Properties
Property Value Source Water Solubility 0.325 mg/mL ALOGPS logP 2.45 ALOGPS logP 2.76 Chemaxon logS -3 ALOGPS pKa (Strongest Acidic) 4.35 Chemaxon pKa (Strongest Basic) -7.1 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 101.93 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 81.69 m3·mol-1 Chemaxon Polarizability 34.38 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-...
- Gene Name
- CACNA2D1
- Uniprot ID
- P54289
- Uniprot Name
- Voltage-dependent calcium channel subunit alpha-2/delta-1
- Molecular Weight
- 124566.93 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-t...
- Gene Name
- CACNA2D2
- Uniprot ID
- Q9NY47
- Uniprot Name
- Voltage-dependent calcium channel subunit alpha-2/delta-2
- Molecular Weight
- 129816.095 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- 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-lactat...
- Gene Name
- SLC5A8
- Uniprot ID
- Q8N695
- Uniprot Name
- Sodium-coupled monocarboxylate transporter 1
- Molecular Weight
- 66577.005 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- Uniprot Name
- Sodium-dependent multivitamin transporter
- Molecular Weight
- 68641.27 Da
References
- 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. [Article]
Drug created at May 02, 2013 21:20 / Updated at February 21, 2021 18:52