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Chemistry

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Also known as: 114-70-5, Sodium 2-phenylacetate, Phenylacetic acid sodium salt, Sodium benzeneacetate, Benzeneacetic acid, sodium salt, Sodium phenylacetate [usan]
Molecular Formula
C8H7NaO2
Molecular Weight
158.13  g/mol
InChI Key
HZOREEUASZHZBI-UHFFFAOYSA-M
FDA UNII
48N6U1781G

Sodium Phenylacetate
Sodium Phenylacetate is the sodium salt form of phenylacetate with ammonia detoxifying activity. Upon administration, sodium phenylacetate binds to glutamine thereby forming phenylacetylglutamine and is thus excreted by the kidneys. By serving as an alternative to urea for the excretion of waste nitrogen, sodium phenylacetate is able to lower ammonia levels in the blood and prevent hyperammonemia.
1 2D Structure

Sodium Phenylacetate

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
sodium;2-phenylacetate
2.1.2 InChI
InChI=1S/C8H8O2.Na/c9-8(10)6-7-4-2-1-3-5-7;/h1-5H,6H2,(H,9,10);/q;+1/p-1
2.1.3 InChI Key
HZOREEUASZHZBI-UHFFFAOYSA-M
2.1.4 Canonical SMILES
C1=CC=C(C=C1)CC(=O)[O-].[Na+]
2.2 Other Identifiers
2.2.1 UNII
48N6U1781G
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Phenylacetate

2. Phenylacetic Acid

3. Phenylacetic Acid, Ammonium Salt

4. Phenylacetic Acid, Calcium Salt

5. Phenylacetic Acid, Cesium Salt

6. Phenylacetic Acid, Lithium Salt

7. Phenylacetic Acid, Mercury Salt

8. Phenylacetic Acid, Potassium Salt

9. Phenylacetic Acid, Rubidium Salt

10. Phenylacetic Acid, Sodium Salt

11. Phenylacetic Acid, Sodium Salt , Carboxy-(11)c-labeled Cpd

2.3.2 Depositor-Supplied Synonyms

1. 114-70-5

2. Sodium 2-phenylacetate

3. Phenylacetic Acid Sodium Salt

4. Sodium Benzeneacetate

5. Benzeneacetic Acid, Sodium Salt

6. Sodium Phenylacetate [usan]

7. Sodium Phenylacetic Acid

8. Nsc-3039

9. 48n6u1781g

10. Sodium 2-phenylethanoate

11. Sodium Phenylacetate;sodium 2-phenylacetate

12. Phenylacetate Sodium Salt

13. Hsdb 5581

14. Acetic Acid, Phenyl-, Sodium Salt

15. Nsc 3039

16. Einecs 204-052-7

17. Phenylessigsaure Natrium-salz [german]

18. Phenylessigsaure Natrium-salz

19. Unii-48n6u1781g

20. Sodium,2-phenylacetate

21. Sodium;2-phenylacetate

22. Schembl62440

23. Chembl1200358

24. Dtxsid8059427

25. Sodium Phenylacetate (jan/usan)

26. Hms2089o12

27. Hms2094m19

28. Sodium Phenylacetate [jan]

29. Sodium Phenylacetate [hsdb]

30. Sodium Phenylacetate [vandf]

31. Sodium Phenylacetate [mart.]

32. Sodium Phenylacetate [who-dd]

33. Akos003052998

34. Akos015890373

35. Sodium Phenylacetate [orange Book]

36. Db-041227

37. Ammonul Component Sodium Phenylacetate

38. Ucephan Component Sodium Phenylacetate

39. D05867

40. Sodium Phenylacetate Component Of Ammonul

41. Sodium Phenylacetate Component Of Ucephan

42. A800813

43. A824291

44. Q27259162

2.4 Create Date
2008-02-05
3 Chemical and Physical Properties
Molecular Weight 158.13 g/mol
Molecular Formula C8H7NaO2
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count2
Rotatable Bond Count2
Exact Mass158.03437374 g/mol
Monoisotopic Mass158.03437374 g/mol
Topological Polar Surface Area40.1 Ų
Heavy Atom Count11
Formal Charge0
Complexity119
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count2
4 Drug and Medication Information
4.1 Therapeutic Uses

Antimetabolites, Antineoplastic

National Library of Medicine's Medical Subject Headings. Phenylacetic acid. Online file (MeSH, 2017). Available from, as of July 12, 2017: https://www.nlm.nih.gov/mesh/2017/mesh_browser/MBrowser.html


/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Chloramphenicol is included in the database.

NIH/NLM; ClinicalTrials.Gov. Available from, as of July 12, 2017: https://clinicaltrials.gov/


Sodium phenylacetate and sodium benzoate injection is indicated as adjunctive therapy in pediatric and adult patients for the treatment of acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzymes of the urea cycle. During acute hyperammonemic episodes, arginine supplementation, caloric supplementation, dietary protein restriction, hemodialysis, and other ammonia lowering therapies should be considered.

NIH; DailyMed. Current Medication Information for Sodium phenylacetate and sodium benzoate injection, solution, concentrate (Updated: February 2016). Available from, as of July 12, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3529be10-0004-4628-9ca1-67a8acd86b51


/Sodium phenylacetate in combination with sodium benzoate/ is indicated as adjunctive therapy for the treatment of acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzymes of the urea cycle. In acute neonatal hyperammonemic coma, in moderate to severe episodes of hyperammonemic encephalopathy, and in episodes of hyperammonemia which fail to respond to an initial course of /Sodium phenylacetate/sodium benzoate/ therapy, hemodialysis is the most rapid and effective technique for removing ammonia. In such cases, the concomitant administration of /Sodium phenylacetate/sodium benzoate/ can help prevent the re-accumulation of ammonia by increasing waste nitrogen excretion. /Included in US product label/

Drug Facts and Comparisons 2015. Clinical Drug Information, LLC St. Louis, MO 2015, p. 678


For more Therapeutic Uses (Complete) data for Sodium phenylacetate (9 total), please visit the HSDB record page.


4.2 Drug Warning

Known hypersensitivity to sodium phenylacetate or sodium benzoate.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017


Plasma ammonia concentrations, neurologic status, laboratory tests, and clinical response should be monitored closely during drug treatment. Because urinary loss of potassium is enhanced by excretion of the non-absorbable anions phenylacetylglutamine and hippurate (conjugation products of phenylacetate and benzoate), plasma potassium concentrations should be carefully monitored and replacement therapy provided when necessary. In addition, serum electrolyte concentrations should be monitored and maintained within the normal range.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017


The Urea Cycle Disorders Conference Group and some experts recommend monitoring plasma concentrations of ammonia scavenging drugs (e.g., sodium phenylacetate and sodium benzoate) to avoid toxicity. In addition, these experts state that written orders for the drugs should be double-checked to avoid overdosage. In the absence of facilities for drug concentration monitoring, the risk of overdosage should be weighed against potential benefits of repeating a loading dose.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017


Each g of sodium phenylacetate provides 6.3 mEq (145 mg) of sodium, and each g of sodium benzoate provides 7 mEq (160 mg of sodium); each mL of injection concentrate labeled as containing 100 mg each of sodium phenylacetate and sodium benzoate provides 1.33 mEq (30.5 mg) of sodium. Sodium phenylacetate and sodium benzoate injection should be used with caution, if at all, in patients with congestive heart failure (CHF), severe renal impairment, or sodium retention with edema. If adverse effects associated with increased sodium concentrations occur, the drug should be discontinued, the patient promptly evaluated, and appropriate measures taken.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017


For more Drug Warnings (Complete) data for Sodium phenylacetate (14 total), please visit the HSDB record page.


5 Pharmacology and Biochemistry
5.1 MeSH Pharmacological Classification

Antimetabolites, Antineoplastic

Antimetabolites that are useful in cancer chemotherapy. (See all compounds classified as Antimetabolites, Antineoplastic.)


5.2 Absorption, Distribution and Excretion

The pharmacokinetics of intravenously administered sodium phenylacetate and sodium benzoate were characterized in healthy adult volunteers. Both benzoate and phenylacetate exhibited nonlinear kinetics. Following 90 minute intravenous infusion mean AUC(last) for benzoate was 20.3, 114.9, 564.6, 562.8, and 1599.1 ug/mL following doses of 1, 2, 3.75, 4, and 5.5 g/sq m, respectively. The total clearance decreased from 5.19 to 3.62 L/h/sq m at the 3.75 and 5.5 g/sq m doses, respectively.

Drug Facts and Comparisons 2015. Clinical Drug Information, LLC St. Louis, MO 2015, p. 678


... Phenylacetate exhibited nonlinear kinetics following the priming dose regimens. AUC(last) was 175.6, 713.8, 2040.6, 2181.6, and 3829.2 ug/hr/mL following doses of 1, 2, 3.75, 4, and 5.5 g/sq m, respectively. The total clearance decreased from 1.82 to 0.89 ug/hr/mL with increasing dose (3.75 and 4 g/sq m, respectively). During the sequence of 90 minute priming infusion followed by a 24 hour maintenance infusion, phenylacetate was detected in the plasma at the end of infusion (Tmax of 2 hr at 3.75 g/sq m) whereas, benzoate concentrations declined rapidly (Tmax of 1.5 hr at 3.75 g/sq m) and were undetectable at 14 and 26 hours following the 3.75 and 4 g/sq m dose, respectively.

Drug Facts and Comparisons 2015. Clinical Drug Information, LLC St. Louis, MO 2015, p. 679


... Phenylacetylglutamine is excreted by the kidneys via glomerular filtration and tubular secretion. ...

Drug Facts and Comparisons 2015. Clinical Drug Information, LLC St. Louis, MO 2015, p. 679


/It is/ not known whether sodium phenylacetate or sodium benzoate or their conjugated metabolites are distributed into milk.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017


For more Absorption, Distribution and Excretion (Complete) data for Sodium phenylacetate (11 total), please visit the HSDB record page.


5.3 Metabolism/Metabolites

Phenylacetate conjugates with glutamine in the liver and kidneys to form phenylacetylglutamine, via acetylation. Phenylacetylglutamine is excreted by the kidneys via glomerular filtration and tubular secretion. The nitrogen content of phenylacetylglutamine per mole is identical to that of urea (both contain 2 moles of nitrogen). ...

Drug Facts and Comparisons 2015. Clinical Drug Information, LLC St. Louis, MO 2015, p. 679


A difference in the metabolic rates for phenylacetate and benzoate was noted. The formation of hippurate from benzoate occurred more rapidly than that of phenylacetylglutamine from phenylacetate, and the rate of elimination for hippurate appeared to be more rapid than that for phenylacetylglutamine.

Drug Facts and Comparisons 2015. Clinical Drug Information, LLC St. Louis, MO 2015, p. 679


Sodium phenylacetate and sodium benzoate are metabolized in the liver.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017


Sodium phenylacetate and sodium benzoate are metabolized in the kidney and phenylacetylglutamine (metabolite of sodium phenylacetate) and hippuric acid (metabolite of sodium benzoate) are mainly excreted in urine.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017


5.4 Mechanism of Action

Sodium phenylacetate and sodium benzoate decrease ammonia concentrations by serving as alternatives to urea for the excretion of waste nitrogen. Phenylacetate is conjugated with glutamine in the liver and kidneys to form phenylacetylglutamine, and benzoate is conjugated with glycine to form hippuric acid; phenylacetylglutamine and hippuric acid subsequently are excreted in urine. Conjugation of 1 mole of phenylacetate with glutamine removes 2 moles of nitrogen, while conjugation of 1 mole of benzoate with glycine removes 1 mole of nitrogen. The nitrogen content of phenylacetylglutamine is identical to that of urea (i.e., both contain 2 moles of nitrogen). Glutamine and glycine used in these reactions are replaced by synthesis, thereby reducing the nitrogen pool and attenuating the risk of ammonia- and glutamine-induced neurotoxicity in patients with deficiencies of urea cycle enzymes.

American Society of Health-System Pharmacists 2017; Drug Information 2017. Bethesda, MD. 2017


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