Information about Sodium benzoate
Sodium benzoate was the first agent developed specifically for the therapy of hyperammonemia caused by urea cycle disorders. Like phenylbutyrate, sodium benzoate acts as an ammonia sink, eliminating nitrogen by an alternative pathways independent of the urea cycle.
Liver safety of Sodium benzoate
Sodium benzoate has not been linked to significant serum enzyme elevations during therapy or to instances of clinically apparent acute liver injury.
Mechanism of action of Sodium benzoate
Sodium benzoate (ben' zoe ate) is a small molecule that conjugates with lysine (an amino acid with one nitrogen molecule) forming hippuric acid which is rapidly excreted by the kidneys and does not require metabolism via the urea cycle. Sodium benzoate is an orphan drug that is approved for the treatment of hyperammonemia in patients with urea cycle disorders, a series of at least 8 rare genetic deficiencies of enzymes involved in the urea cycle and elimination of nitrogen waste. Sodium benzoate has been shown to result in a rapid decrease in serum ammonia levels in children and adults with urea cycle disorders. It is less effective than phenylbutyrate, perhaps because it conjugates to glycine which has a single nitrogen molecule as opposed to phenylbutyrate which conjugates to glutamate which possesses two nitrogens. Nevertheless, because sodium benzoate acts via a different amino acid than phenylbutyrate, the two drugs can be used in combination to treat refractory cases of hyperammonemia due to urea cycle disorders. Indeed, the combination of sodium benzoate with phenylbutyrate was approved for use in the United States in 1996 for the treatment of hyperammonemic crises in children and adults with urea cycle disorders.
Combination with Phenylactetate
The combination of sodium benzoate and phenylacetate is available as a solution for injection in single dose vials (50 mL: 50 mg of each) generically and under the brand name Ammonul. Oral formulations of sodium benzoate are available in other countries of the world. The intravenous preparation is used only to treat hyperammonemic crises with encephalopathy and the dose varies by type of urea cycle disorder and body weight. The intravenous combination of sodium benzoate and phenyl-acetate or -butyrate should be administered only by a physician with expertise in the management of urea cycle disorders. The intravenous infusion should be given via a central and not peripheral line. Common effects of sodium benzoate are nausea, vomiting, injection site reactions, fever, and rash. Because this product is given to patients with severe hyperammonemia who are often critically ill, many of the reported adverse events are more likely due to the underlying conditions rather than the sodium benzoate and phenylbutyrate; they include cardiac arrhythmias, hypoglycemia, respiratory distress and failure, seizures, coma, clonus, liver failure and hyperammonemia.
genetic disorder agents
- gaucher disease agents
glucosylceramide synthase inhibitors (substrate restriction therapy)
lysosomal acid lipase deficiency agents
- agalsidase beta, alglucosidase alfa, alpha1-proteinase inhibitor, elosulfase alfa, galsulfase, idursulfase, laronidase, pegademase
Huntington disease agents
Urea Cycle Disorder Agents