Phenylbutyric acid is an agent indicated for the adjunctive therapy for the management of chronic urea cycle disorders due to deficiencies in specific enzymes, including the neonatal-onset deficiency and late-onset disease with a history of hyperammonemic encephalopathy.

Brand Names
Ammonaps, Buphenyl, Pheburane, Relyvrio
Generic Name
Phenylbutyric acid
DrugBank Accession Number

Phenylbutyric acid is a fatty acid and a derivative of butyric acid naturally produced by colonic bacteria fermentation. It demonstrates a number of cellular and biological effects, such as relieving inflammation and acting as a chemical chaperone.1 It is used to treat genetic metabolic syndromes, neuropathies, and urea cycle disorders.2,3

Small Molecule
Approved, Investigational
Average: 164.2011
Monoisotopic: 164.083729628
Chemical Formula
  • 4-Phenyl-n-butyric acid
  • 4-phenylbutyrate
  • 4-phenylbutyric acid
  • Benzenebutyric acid
  • PBA
  • Phenylbutyrate
  • γ-Phenyl-n-butyric acid
  • γ-phenylbutyric acid
  • ω-Phenylbutanoic acid
  • ω-phenylbutyric acid
External IDs
  • NSC-295



Phenylbutyric acid is used for the treatment of various conditions, including urea cycle disorders, neonatal-onset deficiency, late-onset deficiency disease in patients with a history of hyperammonemic encephalopathy. Phenylbutyric acid must be combined with dietary protein restriction and, in some cases, essential amino acid supplementation.2

Phenylbutyric acid, as sodium phenylbutyrate, is used in combination with tauroursodeoxycholic acid to treat amyotrophic lateral sclerosis (ALS) in adults.3,5

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Associated Conditions
Contraindications & Blackbox Warnings
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Phenylbutyric acid decreases elevated plasma ammonia glutamine levels in patients with urea cycle disorders. It increases waste nitrogen excretion in the form of phenylacetylglutamine.2

In the intestines, phenylbutyric acid was shown to reduce mucosal inflammation, regulate transepithelial fluid transport, and improve oxidative status. Some studies report antineoplastic properties of phenylbutyric acid, showing that phenylbutyric acid can promote growth arrest and apoptosis of cancer cells. It is suggested that phenylbutyric acid can act as an ammonia scavenger, chemical chaperone, and histone deacetylase inhibitor.1

Mechanism of action

Sodium phenylbutyrate is the most commonly used salt used in drug products of phenylbutyric acid. Sodium phenylbutyrate is a pro-drug that rapidly metabolizes to phenylacetate.2 Phenylacetate is conjugated with phenylacetyl-CoA, which in turn combines with glutamine via acetylation to form phenylacetylglutamine. Phenylacetylglutamine is then excreted by the kidneys, thus providing an alternate mechanism of waste nitrogen excretion to the urea cycle.4 Phenylacetylglutamine is comparable to urea, as each molecule contains two moles of nitrogen.2

UAromatic-amino-acid aminotransferaseNot AvailableParacoccus denitrificans
UHistone deacetylase

Following oral administration of a single 5g dose of sodium phenylbutyrate, the Cmax was 195-218 µg/mL under fasting conditions and the Tmax was one hour. The effect of food on drug absorption is unknown.2

Volume of distribution

Not Available

Protein binding

When co-administered with tauroursodeoxycholic acid as a combination product, the in vitro plasma protein binding of phenylbutyric acid is 82%.3


The major sites for metabolism of sodium phenylbutyrate are the liver and kidney.2 Phenylbutyric acid is rapidly metabolized to phenylacetate via beta-oxidation. Phenylacetate is conjugated with phenylacetyl-CoA, which in turn combines with glutamine via acetylation to form phenylacetylglutamine.4

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Route of elimination

Approximately 80–100% of the dose was excreted by the kidneys within 24 hours as the conjugation product, phenylacetylglutamine. For each gram of sodium phenylbutyrate administered, it is estimated that between 0.12–0.15 grams of phenylacetylglutamine nitrogen are produced.2


Following oral administration of a single 5g dose of sodium phenylbutyrate, the elimination half-life of phenylbutyric acid ranged from 0.76 to 0.77 hours.2


Not Available

Adverse Effects
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In animals, lethality was seen at a dose of 1586 mg/kg sodium phenylbutyrate; however, this is a supra-therapeutic dose and acute toxicity is unlikely.4 No adverse experiences have been reported involving overdoses of sodium phenylbutyrate in patients with urea cycle disorders. High levels of phenylacetate, the active metabolite of phenylbutyric acid, can cause nausea, headache, emesis, fatigue, weakness, lethargy, somnolence, dizziness, slurred speech, memory loss, confusion, and disorientation.3

In the event of an overdose, discontinue the drug and institute supportive measures. Hemodialysis or peritoneal dialysis may be beneficial.2 Animal studies in the scientific literature have demonstrated the embryo-fetal toxicity potential of phenylacetate, the major metabolite of phenylbutyrate.3

Not Available
Pharmacogenomic Effects/ADRs
Not Available


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.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Phenylbutyric acid.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Phenylbutyric acid.
AlmotriptanThe metabolism of Almotriptan can be decreased when combined with Phenylbutyric acid.
AlogliptinThe metabolism of Alogliptin can be decreased when combined with Phenylbutyric acid.
AminophenazoneThe metabolism of Aminophenazone can be decreased when combined with Phenylbutyric acid.
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Phenylbutyric acid.
AmoxapineThe metabolism of Amoxapine can be decreased when combined with Phenylbutyric acid.
AmphetamineThe metabolism of Amphetamine can be decreased when combined with Phenylbutyric acid.
AmprenavirThe metabolism of Amprenavir can be decreased when combined with Phenylbutyric acid.
AntipyrineThe metabolism of Antipyrine can be decreased when combined with Phenylbutyric acid.
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Food Interactions
  • Take with food. The effect of food on phenylbutyrate’s absorption is unknown.


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Product Ingredients
IngredientUNIICASInChI Key
Sodium phenylbutyrateNT6K61736T1716-12-7VPZRWNZGLKXFOE-UHFFFAOYSA-M
Product Images
International/Other Brands
triButyrate (Fyrlklövern Scandinavia)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AmmonapsTablet500 mgOralImmedica Pharma Ab2016-09-07Not applicableEU flag
AmmonapsGranule940 mg/gOralImmedica Pharma Ab2016-09-07Not applicableEU flag
AmmonapsTablet500 mgOralImmedica Pharma Ab2016-09-07Not applicableEU flag
AmmonapsGranule940 mg/gOralImmedica Pharma Ab2016-09-07Not applicableEU flag
BuphenylPowder0.94 g/1gOralUcyclyd Pharma Inc.1996-04-302015-02-28US flag
BuphenylPowder0.94 g/1gOralHyperion Therapeutics, Inc.1996-04-302016-11-29US flag
BuphenylTablet500 mg/1OralUcyclyd Pharma Inc.1996-05-132015-02-28US flag
BuphenylPowder0.94 g/1gOralHorizon Therapeutics USA, Inc.1996-04-30Not applicableUS flag
BuphenylTablet500 mg/1OralHyperion Therapeutics, Inc.1996-05-132016-11-29US flag
BuphenylTablet500 mg/1OralHorizon Therapeutics USA, Inc.1996-05-13Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Sodium PhenylbutyratePowder0.94 g/1gOralSigmapharm Laboratories, LLC2013-04-08Not applicableUS flag
Sodium PhenylbutyrateTablet500 mg/1OralMikart, LLC2011-11-182011-11-19US flag
Sodium PhenylbutyratePowder0.94 g/1gOralPar Pharmaceutical2016-08-31Not applicableUS flag
Sodium PhenylbutyrateTablet500 mg/1OralPar Pharmaceutical, Inc.2016-04-29Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
AlbriozaSodium phenylbutyrate (3 g / sachet) + Tauroursodeoxycholic acid (1 g / sachet)Powder, for suspensionOralAmylyx Pharmaceuticals Inc.2022-07-29Not applicableCanada flag
RelyvrioSodium phenylbutyrate (3 g/1) + Tauroursodeoxycholic acid (1 g/1)Powder, for suspensionOralAmylyx Pharmaceuticals Inc2022-09-29Not applicableUS flag


ATC Codes
A16AX03 — Sodium phenylbutyrate
Drug Categories
Chemical TaxonomyProvided by Classyfire
This compound belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
Organic compounds
Super Class
Benzene and substituted derivatives
Sub Class
Not Available
Direct Parent
Benzene and substituted derivatives
Alternative Parents
Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Aromatic homomonocyclic compound / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Monocyclic benzene moiety / Organic oxide / Organic oxygen compound / Organooxygen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monocarboxylic acid (CHEBI:41500)
Affected organisms
Not Available

Chemical Identifiers

CAS number
InChI Key
4-phenylbutanoic acid


General References
  1. Kusaczuk M, Bartoszewicz M, Cechowska-Pasko M: Phenylbutyric Acid: simple structure - multiple effects. Curr Pharm Des. 2015;21(16):2147-66. doi: 10.2174/1381612821666150105160059. [Article]
  2. FDA Approved Drug Products: BUPHENYL (sodium phenylbutyrate) Tablets or Powder, for oral administration [Link]
  3. Health Canada Approved Drug Products: ALBRIOZA (sodium phenylbutyrate and ursodoxicoltaurine) Oral Powder for suspension [Link]
  4. EMA Assessment Report: Pheburane (sodium phenylbutyrate) [Link]
  5. FDA Approved Drug Products: RELYVRIO (sodium phenylbutyrate and taurursodiol) for oral suspension [Link]
Human Metabolome Database
PubChem Compound
PubChem Substance
PDBe Ligand
RxList Drug Page Drug Page
PDB Entries
2ay7 / 3tz2 / 3tz5 / 5vnl / 5vnm / 5vnn / 5yoq

Clinical Trials

Clinical Trials
4CompletedHealth Services ResearchDiabetes / Resistance, Insulin1
4RecruitingTreatmentDeficiencies in enzymes of the urea cycle1
3CompletedTreatmentDeficiencies in enzymes of the urea cycle1
3Not Yet RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2CompletedTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentAmino Acid Metabolism, Inborn Errors1
2CompletedTreatmentAmino Acid Metabolism, Inborn Errors / Argininosuccinic Aciduria / Deficiencies in enzymes of the urea cycle1
2CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS) / Central Nervous System Disorder / Diseases of the Nervous System / MND (Motor Neurone Disease) / Neurodegenerative Disorders / Neuromuscular Disorders / Spinal Cord Diseases / TDP-43 Proteinopathies1
2CompletedTreatmentDeficiencies in enzymes of the urea cycle1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1


Not Available
Not Available
Dosage Forms
Powder, for suspensionOral
GranuleOral940 MG/G
TabletOral500 MG
PowderOral0.94 g/1g
TabletOral500 mg/1
GranuleNot applicable869.6 g/1kg
GranuleOral483 mg / g
GranuleOral483 MG/G
Kit; pelletOral483 mg/1g
PelletOral483 mg/1g
GranuleOral48.3 g
Not Available
Not Available


Experimental Properties
Not Available
Predicted Properties
Water Solubility0.513 mg/mLALOGPS
pKa (Strongest Acidic)4.81Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area37.3 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity46.57 m3·mol-1Chemaxon
Polarizability17.99 Å3Chemaxon
Number of Rings1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available


Mass Spec (NIST)
Not Available
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0udl-7900000000-3308656352d708576a12
MS/MS Spectrum - Quattro_QQQ 10V, NegativeLC-MS/MSsplash10-03di-4900000000-2b18919d21183949b0f0
MS/MS Spectrum - Quattro_QQQ 25V, NegativeLC-MS/MSsplash10-0006-9000000000-6e1432dc108281f8c5fb
MS/MS Spectrum - Quattro_QQQ 40V, NegativeLC-MS/MSsplash10-0006-9100000000-9477dfafb0c27b1670ab
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable


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Paracoccus denitrificans
Pharmacological action
General Function
Pyridoxal phosphate binding
Specific Function
Shows activities toward both dicarboxylic and aromatic substrates.
Gene Name
Uniprot ID
Uniprot Name
Aromatic-amino-acid aminotransferase
Molecular Weight
42731.635 Da
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
Protein group
Pharmacological action
General Function
Transcription regulatory region sequence-specific dna binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...

  1. Kouraklis G, Theocharis S: Histone deacetylase inhibitors: a novel target of anticancer therapy (review). Oncol Rep. 2006 Feb;15(2):489-94. [Article]
  2. Kouraklis G, Theocharis S: Histone deacetylase inhibitors and anticancer therapy. Curr Med Chem Anticancer Agents. 2002 Jul;2(4):477-84. doi: 10.2174/1568011023353921. [Article]
  3. Munshi A, Kurland JF, Nishikawa T, Tanaka T, Hobbs ML, Tucker SL, Ismail S, Stevens C, Meyn RE: Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity. Clin Cancer Res. 2005 Jul 1;11(13):4912-22. doi: 10.1158/1078-0432.CCR-04-2088. [Article]
  4. Ladiges W: The quality control theory of aging. Pathobiol Aging Age Relat Dis. 2014 May 23;4. pii: 24835. doi: 10.3402/pba.v4.24835. eCollection 2014. [Article]
  5. Chang MC, Chen YJ, Lian YC, Chang BE, Huang CC, Huang WL, Pan YH, Jeng JH: Butyrate Stimulates Histone H3 Acetylation, 8-Isoprostane Production, RANKL Expression, and Regulated Osteoprotegerin Expression/Secretion in MG-63 Osteoblastic Cells. Int J Mol Sci. 2018 Dec 17;19(12). pii: ijms19124071. doi: 10.3390/ijms19124071. [Article]

Drug created at September 14, 2010 16:21 / Updated at October 22, 2022 01:06