NameCarglumic Acid
Accession NumberDB06775
TypeSmall Molecule

Carglumic acid is an orphan drug used for the treatment of hyperammonaemia in patients with N-acetylglutamate synthase deficiency. This rare genetic disorder results in elevated blood levels of ammonia, which can eventually cross the blood–brain barrier and cause neurologic problems, cerebral edema, coma, and death. Carglumic acid was approved by the U.S. Food and Drug Administration (FDA) on 18 March 2010.

(2S)-2-(Carbamoylamino)pentanedioic acid
(S)-2-ureidopentanedioic acid
Acide carglumique
Acido carglumico
Acidum carglumicum
Carbamino-L-glutamic acid
Carbamylglutamic acid
L-N-Carbamoylglutamic acid
N-Carbamoyl-L-Glutamic Acid
Ureidoglutaric acid
External IDs OE 312 / OE-312
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CarbagluTablet200 mg/1OralOrphan Europe Sarl2010-03-18Not applicableUs
CarbagluTablet, for suspension200 mgOralOrphan Europe S.A.R.L.2003-01-24Not applicableEu
CarbagluTablet, orally disintegrating200 mgOralOrphan Europe Sarl2015-09-08Not applicableCanada
CarbagluTablet, for suspension200 mgOralOrphan Europe S.A.R.L.2003-01-24Not applicableEu
CarbagluTablet, for suspension200 mgOralOrphan Europe S.A.R.L.2003-01-24Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
CAS number1188-38-1
WeightAverage: 190.154
Monoisotopic: 190.05897144
Chemical FormulaC6H10N2O5
(2S)-2-(carbamoylamino)pentanedioic acid

For the treatment of acute and chronic hyperammonaemia in patients with N-acetylglutamate synthase (NAGS) deficiency. This enzyme is an important component of the urea cycle to prevent build up of neurotoxic ammonium in the blood.

Structured Indications

The median Tmax of Carbaglu was 3 hours (range: 2-4). The initial daily dose ranges from 100 to 250 mg/kg, adjusted thereafter to maintain normal plasma levels of ammonia.

Mechanism of action

Carglumic acid is a synthetic structural analogue of N-acetylglutamate (NAG), which is an essential allosteric activator of the liver enzyme carbamoyl phosphate synthetase 1 (CPS1). CPS1 is found in the mitochondria and is the first enzyme of the urea cycle, which converts ammonia into urea. Carglumic acid acts as a replacement for NAG in NAGS deficiency patients by activating CPS1 but it does not help to regulate the urea cycle.

TargetKindPharmacological actionActionsOrganismUniProt ID
Carbamoyl-phosphate synthase [ammonia], mitochondrialProteinyes
allosteric modulator
HumanP31327 details
Related Articles

30% bioavailability; Cmax, mean, 100 mg/kg dose = 2.6 μg/mL (range of 1.9 - 4.8)
Carglumic acid is not subject to to intracellular degradation.

Volume of distribution

The apparent volume of distribution was 2657 L (range: 1616-5797).

Protein bindingNot Available

A proportion of carglumic acid may be metabolized by the intestinal bacterial flora. The likely end product of carglumic acid metabolism is carbon dioxide, eliminated through the lungs.

Route of elimination

Following administration of a single radiolabeled oral dose of 100 mg/kg of body weight, 9% of the dose was excreted unchanged in the urine and up to 60% of the dose was excreted unchanged in the feces.

Half life

Median values for the terminal half-life was 5.6 hours (range 4.3-9.5).


The apparent total clearance was 5.7 L/min (range 3.0-9.7), the renal clearance was 290 mL/min (range 204-445), and the 24-hour urinary excretion was 4.5 % of the dose (range 3.5-7.5).


LD50, oral, mouse: >1000 mg/kg

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Drug Interactions No interactions found.
Food InteractionsNot Available
Synthesis ReferenceNot Available
General References
  1. Elpeleg O, Shaag A, Ben-Shalom E, Schmid T, Bachmann C: N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy. Ann Neurol. 2002 Dec;52(6):845-9. [PubMed:12447942 ]
  2. Caldovic L, Morizono H, Daikhin Y, Nissim I, McCarter RJ, Yudkoff M, Tuchman M: Restoration of ureagenesis in N-acetylglutamate synthase deficiency by N-carbamylglutamate. J Pediatr. 2004 Oct;145(4):552-4. [PubMed:15480384 ]
  3. Thompson CA: Carglumic acid approved to treat genetic hyperammonemia. Am J Health Syst Pharm. 2010 May 1;67(9):690. doi: 10.2146/news100031. [PubMed:20410539 ]
  4. Haberle J: Role of carglumic acid in the treatment of acute hyperammonemia due to N-acetylglutamate synthase deficiency. Ther Clin Risk Manag. 2011;7:327-32. doi: 10.2147/TCRM.S12703. Epub 2011 Aug 2. [PubMed:21941437 ]
  5. Carbaglu [Link]
External Links
ATC CodesA16AA05 — Carglumic acid
AHFS Codes
  • 40:10
PDB EntriesNot Available
FDA labelDownload (351 KB)
MSDSDownload (82.3 KB)
Clinical Trials
Clinical Trials
2RecruitingTreatmentCarbamoyl-Phosphate Synthase I Deficiency Disease / Late-onset CPS1 Deficiency (CPSD) / Late-onset Ornithine Transcarbamylase Deficiency (OTCD) / Methylmalonic Acidemia / Methylmalonic Acidemia (MMA) / Ornithine Carbamoyltransferase Deficiency / Propionic Acidemia (PA) / Propionic Acidemia, Type I and/or Type II1
2TerminatedTreatmentMethylmalonic Acidemia (MMA) / Propionic Acidemia (PA)1
2WithdrawnTreatmentCarbamyl Phosphate Synthetase Deficiency / Inborn Errors of Metabolism / Methylmalonic Acidemia / Propionic Acidemia (PA) / Urea Cycle Disorders, Inborn1
2, 3RecruitingTreatmentInborn Errors of Metabolism1
3Active Not RecruitingTreatmentMethylmalonic Acidemia / Propionic Acidemia (PA)1
ManufacturersNot Available
PackagersNot Available
Dosage forms
TabletOral200 mg/1
Tablet, for suspensionOral200 mg
Tablet, orally disintegratingOral200 mg
PricesNot Available
PatentsNot Available
Experimental Properties
Predicted Properties
Water Solubility19.1 mg/mLALOGPS
pKa (Strongest Acidic)3.36ChemAxon
pKa (Strongest Basic)-2.3ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area129.72 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity39.41 m3·mol-1ChemAxon
Polarizability16.78 Å3ChemAxon
Number of Rings0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Human Intestinal Absorption-0.8269
Blood Brain Barrier+0.9054
Caco-2 permeable-0.8554
P-glycoprotein substrateNon-substrate0.6682
P-glycoprotein inhibitor INon-inhibitor0.9775
P-glycoprotein inhibitor IINon-inhibitor0.9945
Renal organic cation transporterNon-inhibitor0.9589
CYP450 2C9 substrateNon-substrate0.748
CYP450 2D6 substrateNon-substrate0.8273
CYP450 3A4 substrateNon-substrate0.7701
CYP450 1A2 substrateNon-inhibitor0.9399
CYP450 2C9 inhibitorNon-inhibitor0.9371
CYP450 2D6 inhibitorNon-inhibitor0.955
CYP450 2C19 inhibitorNon-inhibitor0.9447
CYP450 3A4 inhibitorNon-inhibitor0.8408
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9909
Ames testNon AMES toxic0.8509
BiodegradationReady biodegradable0.912
Rat acute toxicity1.3576 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9741
hERG inhibition (predictor II)Non-inhibitor0.9818
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Mass Spec (NIST)Not Available
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-000j-0900000000-b40c000081e1b7470cc1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-002b-0900000000-eb1fe6fcbdc6f376370eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0udi-0900000000-245f4056f629592bd99fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0udi-4900000000-3a5f21eb40fd1821e24fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0pb9-9500000000-67aafe80496b10392ef0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
DescriptionThis compound belongs to the class of chemical entities known as glutamic acid and derivatives. These are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassCarboxylic acids and derivatives
Direct ParentGlutamic acid and derivatives
Alternative ParentsFatty acids and conjugates / Dicarboxylic acids and derivatives / Isoureas / Carboxylic acids / Carboximidamides / Organopnictogen compounds / Organic oxides / Imines / Hydrocarbon derivatives / Carbonyl compounds
SubstituentsGlutamic acid or derivatives / Dicarboxylic acid or derivatives / Fatty acid / Isourea / Carboximidamide / Carboxylic acid / Carboximidic acid derivative / Organic oxide / Organic nitrogen compound / Hydrocarbon derivative
Molecular FrameworkAliphatic acyclic compounds
External Descriptorsureas, N-acyl-L-glutamic acid (CHEBI:71028 )


Pharmacological action
allosteric modulator
General Function:
Phospholipid binding
Specific Function:
Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.
Gene Name:
Uniprot ID:
Uniprot Name:
Carbamoyl-phosphate synthase [ammonia], mitochondrial
Molecular Weight:
164938.145 Da
  1. Authors unspecified: Carglumic acid: a second look. Confirmed progress in a rare urea cycle disorder. Prescrire Int. 2008 Apr;17(94):50-1. [PubMed:18516804 ]
  2. Hart EJ, Powers-Lee SG: Role of Cys-1327 and Cys-1337 in redox sensitivity and allosteric monitoring in human carbamoyl phosphate synthetase. J Biol Chem. 2009 Feb 27;284(9):5977-85. doi: 10.1074/jbc.M808702200. Epub 2008 Dec 23. [PubMed:19106093 ]
  3. Kasapkara CS, Ezgu FS, Okur I, Tumer L, Biberoglu G, Hasanoglu A: N-carbamylglutamate treatment for acute neonatal hyperammonemia in isovaleric acidemia. Eur J Pediatr. 2011 Jun;170(6):799-801. doi: 10.1007/s00431-010-1362-9. Epub 2011 Jan 5. [PubMed:21207059 ]
Drug created on September 14, 2010 10:21 / Updated on June 24, 2017 13:27