Medication Summary

Sodium benzoate and sodium phenylacetate may reduce ammonia levels by providing an alternative pathway.

Class Summary

These agents assist in excreting nitrogen and serve as an alternative to urea in reducing waste nitrogen levels. Administer only in a large medical facility with close laboratory monitoring available.

Sodium phenylacetate and sodium benzoate (Ammonul, Ucephan)

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Benzoate combines with glycine to form hippurate, which is excreted in urine. One mol of benzoate removes 1 mol of nitrogen. Phenylacetate conjugates (via acetylation) glutamine in the liver and kidneys to form phenylacetylglutamine, which is excreted by the kidneys. The nitrogen content of phenylacetylglutamine per mole is identical to that of urea (2 mol of nitrogen). Ammonul must be administered with arginine for carbamyl phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthetase, or argininosuccinate lyase deficiencies. Indicated as adjunctive treatment of acute hyperammonemia associated with encephalopathy caused by urea-cycle enzyme deficiencies. Serves as an alternative to urea to reduce waste nitrogen levels.

Glycerol phenylbutyrate (Ravicti)

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Glycerol phenylbutyrate is a nitrogen-binding agent for chronic management of adult and pediatric patients (including newborns) with urea cycle disorders who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. It is a pre-prodrug that is metabolized by ester hydrolysis and pancreatic lipases to phenylbutyrate and then by beta oxidation to phenylacetate. Glutamine is conjugated with phenylacetate to form phenylacetylglutamine, a nitrogen waste product that is excreted in the urine. It is not indicated for treatment of hyperammonemia.

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Media Gallery

Important products and enzymes in ornithine metabolism (see text for pathway detail). Enzymes and transporters are highlighted in italics.

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Author

Richard E Frye, MD, PhD Professor of Child Health, University of Arizona College of Medicine at Phoenix; Chief of Neurodevelopmental Disorders, Director of Autism and Down Syndrome and Fragile X Programs, Division of Neurodevelopmental Disorders, Department of Neurology, Barrow Neurological Institute at Phoenix Children's Hospital

Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society

Disclosure: Nothing to disclose.

Coauthor(s)

Paul J Benke, MD, PhD Director, Division of Clinical Genetics, Joe DiMaggio Children's Hospital

Paul J Benke, MD, PhD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Robert D Steiner, MD, FAAP, FACMG Professor (Clinical), Department of Pediatrics, University of Wisconsin School of Medicine and Public Health; Editor-in-Chief, Genetics in Medicine; Chief Medical Officer, PreventionGenetics

Robert D Steiner, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics and Genomics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: PreventionGenetics-part of Exact Sciences; Acer Therapeutics; DNARx; Best Doctors; PTC Therapeutics; CTX Alliance; Leadiant' Travere<br/>Received income in an amount equal to or greater than $250 from: Marshfield Clinic; PreventionGenetics-part of Exact Sciences; Acer Therapeutics; PTC Therapeutics; DNARx; Leadiant; Travere.