Identification

Summary

Triheptanoin is triheptanoin is a medium chain triglyceride indicated to provide calories and fatty acids to treat long chain fatty acid oxidation disorders.

Brand Names
Dojolvi
Generic Name
Triheptanoin
DrugBank Accession Number
DB11677
Background

Triheptanoin is a source of heptanoate fatty acids, which can be metabolized without the enzymes of long chain fatty acid oxidation.4 In clinical trials, patients with long chain fatty acid oxidation disorders (lc-FAODs) treated with triheptanoin are less likely to develop hypoglycemia, cardiomyopathy, rhabdomyolysis, and hepatomegaly.1,2 Complications in lc-FAOD patients are reduced from approximately 60% to approximately 10% with the addition of triheptanoin.2

Triheptanoin was granted FDA approval on 30 June 2020.4

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 428.61
Monoisotopic: 428.313789137
Chemical Formula
C24H44O6
Synonyms
  • Glycerol triheptanoate
  • Glyceryl triheptanoate
  • Trienanthoin
  • Triheptanoic glyceride
  • Triheptanoin
  • Triheptylin
  • Trioenanthoin
External IDs
  • UX-007
  • UX007

Pharmacology

Indication

Triheptanoin is a medium chain triglyceride indicated to provide calories and fatty acids to treat long chain fatty acid oxidation disorders (lc-FAODs).4

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Triheptanoin is a source of medium chain fatty acids for patients with lc-FAODs.4 It has a moderate duration of action and a wide therapeutic window.4 Patients should be counselled regarding the risk of feeding tube dysfunction and intestinal malabsorption due to pancreatic insufficiency.4

Mechanism of action

Triheptanoin is a source of heptanoate fatty acids, which can be metabolized without the enzymes of long chain fatty acid oxidation.4 In clinical trials, patients with lc-FAODs treated with triheptanoin experienced improvements in hypoglycemia, cardiomyopathy, and rhabdomyolysis.1

Absorption

A single 0.3 g/kg dose of triheptanoin reaches a Cmax of 178.9 µmol/L, with a Tmax 0.5 h, and an AUC of 336.5 µmol*h/L.4 A single 0.4 g/kg dose of triheptanoin reaches a Cmax of 259.1 µmol/L, with a Tmax 0.8 h, and an AUC of 569.1 µmol*h/L.4

Volume of distribution

Not Available

Protein binding

Triheptanoin is approximately 80% protein bound in plasma,4 likely serum albumin.3

Metabolism

Triheptanoin is hydrolysed to heptanoate, which can be further metabolized to β-hydroxypentanoate or β-hydroxybutyrate.4

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Route of elimination

Triheptanoin is minimally eliminated in the urine.4

Half-life

Due to multiple peak concentrations of the heptanoate metabolite, the half life of triheptanoin could not be determined.4

Clearance

A single dose of 0.3 g/kg results in a mean apparent clearance of 6.05 L/h/kg for heptanoate.4 A single dose of 0.4 g/kg results in a mean apparent clearance of 4.31 L/h/kg for heptanoate.4

Adverse Effects
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Toxicity

Not Available

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.
DrugInteraction
OrlistatOrlistat can cause a decrease in the absorption of Triheptanoin resulting in a reduced serum concentration and potentially a decrease in efficacy.
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Food Interactions
  • Take with food. Take triheptanoin with food, liquid, or formula.

Products

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International/Other Brands
Dojolvi
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DojolviLiquid0.96 g/1mLOralUltragenyx Pharmaceutical Inc.2020-07-01Not applicableUS flag
DojolviLiquid100 % w/wOralUltragenyx Pharmaceutical Inc2021-04-01Not applicableCanada flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as triacylglycerols. These are glycerides consisting of three fatty acid chains covalently bonded to a glycerol molecule through ester linkages.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Glycerolipids
Sub Class
Triradylcglycerols
Direct Parent
Triacylglycerols
Alternative Parents
Tricarboxylic acids and derivatives / Fatty acid esters / Carboxylic acid esters / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Aliphatic acyclic compound / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Fatty acid ester / Fatty acyl / Hydrocarbon derivative / Organic oxide / Organic oxygen compound / Organooxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans

Chemical Identifiers

UNII
2P6O7CFW5K
CAS number
620-67-7
InChI Key
PJHKBYALYHRYSK-UHFFFAOYSA-N
InChI
InChI=1S/C24H44O6/c1-4-7-10-13-16-22(25)28-19-21(30-24(27)18-15-12-9-6-3)20-29-23(26)17-14-11-8-5-2/h21H,4-20H2,1-3H3
IUPAC Name
1,3-bis(heptanoyloxy)propan-2-yl heptanoate
SMILES
CCCCCCC(=O)OCC(COC(=O)CCCCCC)OC(=O)CCCCCC

References

General References
  1. Wehbe Z, Tucci S: Therapeutic potential of triheptanoin in metabolic and neurodegenerative diseases. J Inherit Metab Dis. 2020 May;43(3):385-391. doi: 10.1002/jimd.12199. Epub 2019 Dec 12. [Article]
  2. Roe CR, Brunengraber H: Anaplerotic treatment of long-chain fat oxidation disorders with triheptanoin: Review of 15 years Experience. Mol Genet Metab. 2015 Dec;116(4):260-8. doi: 10.1016/j.ymgme.2015.10.005. Epub 2015 Oct 24. [Article]
  3. van der Vusse GJ: Albumin as fatty acid transporter. Drug Metab Pharmacokinet. 2009;24(4):300-7. doi: 10.2133/dmpk.24.300. [Article]
  4. FDA Approved Drug Products: Dojolvi Triheptanoin Oral Liquid [Link]
PubChem Compound
69286
PubChem Substance
347828045
ChemSpider
62497
RxNav
1313234
ChEMBL
CHEMBL4297585
ZINC
ZINC000004521897
Wikipedia
Triheptanoin
FDA label
Download (385 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3TerminatedTreatmentGlucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)1
3WithdrawnTreatmentLong-chain Fatty Acid Transport Deficiency1
2Active Not RecruitingTreatmentEpilepsies / Glucose Transport Defect / Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS) / Glut1 Deficiency Syndrome 1, Autosomal Recessive / GLUT1DS1 / Metabolism Disorder, Glucose1
2Active Not RecruitingTreatmentGlucose Transporter Type 1 Deficiency Syndrome (Glut1 DS) / GLUT1DS11
2CompletedTreatmentAdult Polyglucosan Body Disease / Glycogen Brancher Enzyme Deficiency / Glycogen Storage Disease Type IV1
2CompletedTreatmentAlternating Hemiplegia of Childhood1
2CompletedTreatmentCarnitine Palmitoyltransferase (CPT I or CPT II) Deficiency / Carnitine-acylcarnitine Translocase (CACT) Deficiency / Long-chain 3 hydroxyacylCoA Dehydrogenase (LCHAD) Deficiency / Trifunctional Protein (TFP) Deficiency / Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency1
2CompletedTreatmentCarnitine Palmitoyltransferase (CPT II) Deficiency / Long-chain 3 hydroxyacylCoA Dehydrogenase (LCHAD) Deficiency / Long-chain Fatty Acid Oxidation Disorders (LC-FAOD) / Trifunctional Protein (TFP) Deficiency / Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency1
2CompletedTreatmentCarnitine Palmitoyltransferase 2 (CPT2) Deficiency / Long-chain 3 hydroxyacylCoA Dehydrogenase (LCHAD) Deficiency / Mitochondrial Trifunctional Protein (TFP) Deficiency / Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency1
2CompletedTreatmentGlucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
LiquidOral0.96 g/1mL
LiquidOral100 % w/w
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9186344No2015-11-172025-07-01US flag
US8697748No2014-04-152025-10-03US flag

Properties

State
Liquid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000415 mg/mLALOGPS
logP6.42ALOGPS
logP6.92ChemAxon
logS-6ALOGPS
pKa (Strongest Basic)-6.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area78.9 Å2ChemAxon
Rotatable Bond Count23ChemAxon
Refractivity117.06 m3·mol-1ChemAxon
Polarizability52.67 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. van der Vusse GJ: Albumin as fatty acid transporter. Drug Metab Pharmacokinet. 2009;24(4):300-7. doi: 10.2133/dmpk.24.300. [Article]

Drug created at October 20, 2016 20:39 / Updated at August 09, 2022 10:05