Sodium phenylbutyrate (Ammonaps) has been licensed as an "orphan drug" for adjunctive therapy in the chronic management of urea cycle disorders. These disorders are deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase or argininosuccinate synthetase.
Sodium phenylbutyrate is indicated for all patients with neonatal onset presentation (complete enzyme deficiencies presenting within the first 28 days of life), and for patients with late onset disease (partial enzyme deficiencies, presenting after the first month of life) who have a history of hyperammanaemic encephalopathy. Orphan Europe, manufacturer of Ammonaps, says that, in the UK, around 18 babies are born with this condition each year.
The company says that the urea cycle is a self-regenerating pathway or cycle by which all of the body's waste nitrogen is converted into urea for renal excretion. An enzyme defect in the cycle leads to a greatly reduced capacity of the cycle to metabolise waste nitrogen. This may lead to seizures, coma and death.
Sodium phenylbutyrate, previously available on a named-patient basis, is a prodrug which is rapidly metabolised to phenyl-acetate. Phenylacetate binds to glutamine to form phenylacetylglutamine, which is then excreted by the kidney, reducing elevated plasma ammonia and glutamine levels.