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Identification
- Summary
Vigabatrin is an irreversible GABA transaminase inhibitor used as an adjunct therapy to treat refractory complex partial seizures in patients ≥2 years unresponsive to alternatives. May also be used as monotherapy to treat infantile spasms in infants 1 month to 2 years.
- Brand Names
- Sabril, Vigadrone, Vigafyde, Vigpoder
- Generic Name
- Vigabatrin
- DrugBank Accession Number
- DB01080
- Background
Vigabatrin is an analog of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system, used in the treatment of refractory seizures and infantile spasms.7 It irreversibly inhibits the enzyme responsible for GABA metabolism, thereby increasing levels of circulating GABA. Although administered as a racemic mixture, only the S(+) enantiomer is pharmacologically active.4
It was first introduced as an antiepileptic agent in the United Kingdom in 1989 and was used extensively until 1997, when an association with vision loss became apparent.6 Its use is now generally reserved for patients who have failed alternative therapies, and its US approval by the FDA in 2009 mandated the creation of a drug registry to monitor patients for visual deficits.9,6
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Vigabatrin (DB01080)
- Weight
- Average: 129.157
Monoisotopic: 129.078978601 - Chemical Formula
- C6H11NO2
- Synonyms
- 4-Amino-5-hexenoic acid
- Gamma vinyl GABA
- gamma-Vinyl GABA
- gamma-Vinyl-gamma-aminobutyric acid
- GVG
- Vigabatrin
- Vigabatrina
- Vigabatrine
- Vigabatrinum
- Vinyl gamma-aminobutyric acid
- External IDs
- CPP-109
- MDL 71,754
- MDL-71754
- RMI-71754
Pharmacology
- Indication
Vigabatrin is indicated as adjunctive therapy in the treatment of refractory complex partial seizures in patients 2 years of age and older who have had inadequate responses to multiple previous treatments (i.e. not to be used for first-line therapy).7 It is also indicated as monotherapy in the treatment of infantile spasms in patients between 1 month and 2 years of age for whom the potential benefits outweigh the risk of vision loss.7
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Infantile spasms (is) •••••••••••• •••••• Adjunct therapy in treatment of Refractory complex partial seizures •••••••••••• •••••••••• •••••••• •• ••••••• ••••••••••• •••••••••• ••••••• ••• ••••••••• •••••• - Contraindications & Blackbox Warnings
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Vigabatrin is an antiepileptic agent chemically unrelated to other anticonvulsants. Vigabatrin prevents the metabolism of GABA by irreversibly inhibiting GABA transaminase (GABA-T). As vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), its duration of effect is thought to be dependent on the rate of GABA-T re-synthesis rather than on the rate of drug elimination.7
- Mechanism of action
Gamma-aminobutyric acid (GABA) is the major inhibitory transmitter throughout the central nervous system, and the potentiation of GABAergic neurotransmission is therefore a crucial mechanism through which antiepileptic agents may combat the pathologic excitatory neurotransmission seen in epilepsy.5 Vigabatrin increases concentrations of GABA in the central nervous system by irreversibly inhibiting the enzymes responsible for its metabolism to succinic semialdehyde: gamma-aminobutyric acid transaminase (GABA-T).7
Target Actions Organism A4-aminobutyrate aminotransferase, mitochondrial inhibitorHumans - Absorption
Absorption following oral administration is essentially complete.7 The Tmax is approximately 2.5 hours in infants (5m - 2y) and 1 hour in all other age groups.
- Volume of distribution
Vigabatrin is widely distributed throughout the body with a mean steady-state volume of distribution of 1.1 L/kg.7
- Protein binding
Vigabatrin does not bind to plasma proteins.7
- Metabolism
Vigabatrin is not metabolized to any significant extent.7
- Route of elimination
Approximately 95% of the drug is eliminated in the urine within 72 hours of administration, of which ~80% is unchanged parent drug.7
- Half-life
The terminal half-life of vigabatrin is approximately 5.7 hours for infants (5m - 2y), 6.8 hours for children (3y - 9y), 9.5 hours for adolescents (10y - 16y), and 10.5 h for adults.7
- Clearance
The oral clearance of vigabatrin is 2.4 L/h for infants (5m - 2y), 5.1 L/h for children (3y - 9y), 5.8 L/h for adolescents (10y - 16y), and 7 L/h for adults.7
- Adverse Effects
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The oral LD50 of vigabatrin in mice and rats is 2830 mg/kg and 3100 mg/kg, respectively.8 Symptoms of overdose tend to involve significant CNS depression - e.g. coma, unconsciousness, and/or drowsiness - with less common symptoms including neurologic disorders (e.g. seizure activity, speech disorder, headache) and psychiatric sequelae (e.g. psychosis, agitation, abnormal behaviour, confusion).7
In cases of overdose, symptoms generally resolve with symptomatic and supportive care. Standard measures to remove unabsorbed drug may be employed (e.g. gastric lavage), although an in vitro study found that activated charcoal did not significantly absorb vigabatrin.7 Although vigabatrin is not protein-bound, the effectiveness of hemodialysis in drug removal during overdose is unknown - isolated reports of patients in renal failure undergoing hemodialysis who were receiving therapeutic doses of vigabatrin note a reduction in vigabatrin plasma concentrations of 40-60% following dialysis.7
- 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 CNS depression can be increased when Vigabatrin is combined with 1,2-Benzodiazepine. Acetazolamide The risk or severity of CNS depression can be increased when Acetazolamide is combined with Vigabatrin. Acetophenazine The risk or severity of CNS depression can be increased when Acetophenazine is combined with Vigabatrin. Agomelatine The risk or severity of CNS depression can be increased when Vigabatrin is combined with Agomelatine. Alfentanil The risk or severity of CNS depression can be increased when Alfentanil is combined with Vigabatrin. - Food Interactions
- Take with or without food.
- Take with plain water. Only mix vigabatrin oral solution powder with plain water.
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.- International/Other Brands
- Sabrilan (Lundbeck Inc. ) / Sabrilex (Lundbeck Inc. )
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Kigabeq Tablet 100 mg Oral Orphelia Pharma Sas 2020-12-16 Not applicable EU 
Kigabeq Tablet 500 mg Oral Orphelia Pharma Sas 2020-12-16 Not applicable EU Sabril Powder, for solution 50 mg/1mL Oral Lundbeck Pharmaceuticals Llc 2009-08-21 Not applicable US 
Sabril Tablet 500 mg Oral Lundbeck Pharmaceuticals Llc 1994-12-31 Not applicable Canada 
Sabril Tablet, film coated 500 mg/1 Oral Lundbeck Pharmaceuticals Llc 2009-08-21 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Vigabatrin Tablet 500 mg/1 Oral Edenbridge Pharmaceuticals LLC. 2022-06-29 Not applicable US Vigabatrin Powder, for solution 50 mg/1mL Oral Ascend Laboratories, LLC 2020-12-03 Not applicable US Vigabatrin Powder, for solution 500 mg/10mL Oral Biocon Pharma Inc. 2022-08-29 Not applicable US Vigabatrin Tablet, film coated 500 mg/1 Oral Actavis Pharma, Inc. 2019-02-06 Not applicable US Vigabatrin Powder, for solution 500 mg/1 Oral Padagis US LLC 2022-06-29 Not applicable US
Categories
- ATC Codes
- N03AG04 — Vigabatrin
- Drug Categories
- Acids, Acyclic
- Aminobutyrates
- Anti-epileptic Agent
- Anticonvulsants
- Butyrates
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2C9 Inducers
- Cytochrome P-450 CYP2C9 Inducers (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Enzyme Inhibitors
- Fatty Acid Derivatives
- Fatty Acids
- GABA Agents
- Lipids
- Miscellaneous Anticonvulsants
- Nervous System
- Neurotransmitter Agents
- 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
- Medium-chain fatty acids / Amino fatty acids / Unsaturated fatty acids / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives show 1 more
- Substituents
- Aliphatic acyclic compound / Amine / Amino acid / Amino fatty acid / Carbonyl group / Carboxylic acid / Fatty acid / Fatty acyl / Gamma amino acid or derivatives / Hydrocarbon derivative show 11 more
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- gamma-amino acid (CHEBI:63638)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- GR120KRT6K
- CAS number
- 68506-86-5
- InChI Key
- PJDFLNIOAUIZSL-UHFFFAOYSA-N
- InChI
- InChI=1S/C6H11NO2/c1-2-5(7)3-4-6(8)9/h2,5H,1,3-4,7H2,(H,8,9)
- IUPAC Name
- 4-aminohex-5-enoic acid
- SMILES
- NC(CCC(O)=O)C=C
References
- General References
- Gram L, Larsson OM, Johnsen A, Schousboe A: Experimental studies of the influence of vigabatrin on the GABA system. Br J Clin Pharmacol. 1989;27 Suppl 1:13S-17S. [Article]
- Zwanzger P, Baghai TC, Schuele C, Strohle A, Padberg F, Kathmann N, Schwarz M, Moller HJ, Rupprecht R: Vigabatrin decreases cholecystokinin-tetrapeptide (CCK-4) induced panic in healthy volunteers. Neuropsychopharmacology. 2001 Nov;25(5):699-703. [Article]
- Tulloch JK, Carr RR, Ensom MH: A systematic review of the pharmacokinetics of antiepileptic drugs in neonates with refractory seizures. J Pediatr Pharmacol Ther. 2012 Jan;17(1):31-44. doi: 10.5863/1551-6776-17.1.31. [Article]
- Jacqz-Aigrain E, Guillonneau M, Rey E, Macher MA, Montes C, Chiron C, Loirat C: Pharmacokinetics of the S(+) and R(-) enantiomers of vigabatrin during chronic dosing in a patient with renal failure. Br J Clin Pharmacol. 1997 Aug;44(2):183-5. doi: 10.1046/j.1365-2125.1997.00636.x. [Article]
- Davies JA: Mechanisms of action of antiepileptic drugs. Seizure. 1995 Dec;4(4):267-71. doi: 10.1016/s1059-1311(95)80003-4. [Article]
- Foroozan R: Vigabatrin: Lessons Learned From the United States Experience. J Neuroophthalmol. 2018 Dec;38(4):442-450. doi: 10.1097/WNO.0000000000000609. [Article]
- FDA Approved Drug Products: Sabril (vigabatrin) for oral use [Link]
- Health Canada Product Monograph: Sabril (vigabatrin) for oral use [Link]
- Vigabatrin REMS Program [Link]
- External Links
- Human Metabolome Database
- HMDB0015212
- KEGG Drug
- D00535
- KEGG Compound
- C07500
- PubChem Compound
- 5665
- PubChem Substance
- 46507052
- ChemSpider
- 5463
- BindingDB
- 50118886
- 14851
- ChEBI
- 63638
- ChEMBL
- CHEMBL89598
- Therapeutic Targets Database
- DAP000557
- PharmGKB
- PA10231
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Vigabatrin
- MSDS
- Download (63.9 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Epilepsy 1 somestatus stop reason just information to hide Not Available Completed Not Available Infantile Spasms (IS) / Refractory Complex Partial Seizures in Adults 1 somestatus stop reason just information to hide Not Available Completed Treatment Infantile Spasms (IS) 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Epilepsy 1 somestatus stop reason just information to hide Not Available Recruiting Treatment Infantile Spasms (IS) / West's syndrome 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Lundbeck Inc.
- Dosage Forms
Form Route Strength Tablet Oral 500.00 mg Tablet Oral 100 mg Tablet, soluble Oral 100 MG Tablet, soluble Oral 500 MG Granule, for solution Oral 1 G Granule, for solution Oral 500 MG Powder, for solution Oral 50 mg/1mL Powder, for solution Oral 500 mg / sachet Tablet Oral 500 mg Tablet, film coated Oral 500 mg/1 Tablet, coated Oral 500 mg Tablet, film coated Oral Powder, for solution Oral Powder Oral 1 g / pck Powder Oral 2 g / pck Powder Oral 3 g / pck Tablet, film coated Oral 500 mg For solution Oral 500 mg/1 Powder, for solution Oral 500 mg/1mL Powder, for solution Oral 500 mg/10mL Powder, for solution Oral 500 mg/1 Tablet Oral 500 mg/1 For solution Oral 50 mg/1mL Solution Oral 100 mg/1mL Tablet Oral 500.000 mg - Prices
Unit description Cost Unit Sabril 500 mg tablet 16.66USD tablet Sabril 500 mg Powder Packet 0.95USD packet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US12016857 No 2019-08-16 2039-08-16 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 171-176C FDA Label water solubility 55.1 mg/mL FDA Label logP -1.96 FDA Label pKa 4 and 9.7 FDA Label - Predicted Properties
Property Value Source Water Solubility 96.6 mg/mL ALOGPS logP -2.6 ALOGPS logP -2.1 Chemaxon logS -0.13 ALOGPS pKa (Strongest Acidic) 4.61 Chemaxon pKa (Strongest Basic) 9.91 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 63.32 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 34.29 m3·mol-1 Chemaxon Polarizability 13.64 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9213 Blood Brain Barrier + 0.9382 Caco-2 permeable - 0.5191 P-glycoprotein substrate Non-substrate 0.797 P-glycoprotein inhibitor I Non-inhibitor 0.949 P-glycoprotein inhibitor II Non-inhibitor 0.9856 Renal organic cation transporter Non-inhibitor 0.8944 CYP450 2C9 substrate Non-substrate 0.8785 CYP450 2D6 substrate Non-substrate 0.8115 CYP450 3A4 substrate Non-substrate 0.7664 CYP450 1A2 substrate Non-inhibitor 0.9149 CYP450 2C9 inhibitor Non-inhibitor 0.9389 CYP450 2D6 inhibitor Non-inhibitor 0.9654 CYP450 2C19 inhibitor Non-inhibitor 0.963 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9824 Ames test Non AMES toxic 0.8409 Carcinogenicity Non-carcinogens 0.7678 Biodegradation Ready biodegradable 0.7494 Rat acute toxicity 1.6656 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9617 hERG inhibition (predictor II) Non-inhibitor 0.9772
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 126.7484955 predictedDarkChem Lite v0.1.0 [M-H]- 122.93974 predictedDeepCCS 1.0 (2019) [M+H]+ 127.7946955 predictedDarkChem Lite v0.1.0 [M+H]+ 125.88866 predictedDeepCCS 1.0 (2019) [M+Na]+ 127.2032955 predictedDarkChem Lite v0.1.0 [M+Na]+ 134.58556 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively (PubMed:10407778, PubMed:15528998). Can also convert delta-aminovalerate and beta-alanine (By similarity)
- Specific Function
- (S)-3-amino-2-methylpropionate transaminase activity
- Gene Name
- ABAT
- Uniprot ID
- P80404
- Uniprot Name
- 4-aminobutyrate aminotransferase, mitochondrial
- Molecular Weight
- 56438.405 Da
References
- Weber OM, Verhagen A, Duc CO, Meier D, Leenders KL, Boesiger P: Effects of vigabatrin intake on brain GABA activity as monitored by spectrally edited magnetic resonance spectroscopy and positron emission tomography. Magn Reson Imaging. 1999 Apr;17(3):417-25. [Article]
- Valdizan EM, Garcia AP, Armijo JA: Effects of increasing doses of vigabatrin on platelet gamma-aminobutyric acid-transaminase and brain gamma-aminobutyric acid in rats. Eur J Pharmacol. 1999 Mar 19;369(2):169-73. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- FDA Approved Drug Products: Sabril (vigabatrin) for oral use [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- FDA Approved Drug Products: Sabril (vigabatrin) for oral use [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Electrogenic proton/amino acid symporter with selectivity for small apolar L-amino acids, their D-enantiomers and selected amino acid derivatives such as 4-aminobutanoate/GABA (PubMed:12527723, PubMed:12809675, PubMed:19549785). May be involved in the efflux from the lysosomal compartment of neutral amino acids resulting from proteolysis (By similarity). May play a role in specifying sites for exocytosis in neurons (By similarity)
- Specific Function
- alanine transmembrane transporter activity
- Gene Name
- SLC36A1
- Uniprot ID
- Q7Z2H8
- Uniprot Name
- Proton-coupled amino acid transporter 1
- Molecular Weight
- 53075.045 Da
References
- Abbot EL, Grenade DS, Kennedy DJ, Gatfield KM, Thwaites DT: Vigabatrin transport across the human intestinal epithelial (Caco-2) brush-border membrane is via the H+ -coupled amino-acid transporter hPAT1. Br J Pharmacol. 2006 Feb;147(3):298-306. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 03, 2024 04:54