Urea-cycle disorders are a group of rare hereditary
metabolic diseases characterized by deficiencies of one of the
enzymes and transporters involved in the
urea cycle, which is necessary for the removal of
nitrogen produced from
protein breakdown. These hereditary
metabolic diseases are characterized by
hyperammonemia and life-threatening hyperammonemic crises. Pharmacological treatment of
urea-cycle disorders involves alternative
nitrogen-scavenging pathways.
Sodium benzoate combines with
glycine and
phenylacetate/phenylbutyrate with
glutamine, forming, respectively,
hippuric acid and
phenylacetylglutamine, which are eliminated in the urine. Among the
ammonia-scavenging drugs,
sodium phenylbutyrate is a well-known long-term treatment of
urea-cycle disorders. It has been used since 1987 as an
investigational new drug, and was approved for marketing in the US in 1996 and the EU in 1999. However,
sodium phenylbutyrate has an aversive odor and taste, which may compromise patients' compliance, and many patients have reported difficulty in taking this
drug.
Sodium phenylbutyrate granules are a new tasteless and odor-free formulation of
sodium phenylbutyrate, which is indicated in the treatment of
urea-cycle disorders. This recently developed taste-masked formulation of
sodium phenylbutyrate granules was designed to overcome the considerable issues that taste has on adherence to
therapy. Several studies have reported the clinical experience of patients with
urea-cycle disorders treated with this new tasteless formulation of
sodium phenylbutyrate. Analysis of the data indicated that this taste-masked formulation of
sodium phenylbutyrate granules improved quality of life for
urea-cycle disorder patients. Furthermore, a postmarketing report on the use of the product has confirmed the previous observations of improved compliance, efficacy, and safety with this taste-masked formulation of
sodium phenylbutyrate.