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AHFS/Drugs.com | Consumer Drug Information |
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Pharmacokinetic data | |
Metabolism | to phenylacetic acid |
Elimination half-life | 0.8 hours |
Excretion | 80% as phenylacetylglutamine |
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ECHA InfoCard | 100.130.318 |
Chemical and physical data | |
Formula | C10H11NaO2 |
Molar mass | 186.2 g/mol g·mol−1 |
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Sodium phenylbutyrate is an orphan drug, marketed by Ucyclyd Pharma (Hunt Valley, USA) under the trade name Buphenyl, by Swedish Orphan International (Sweden) as Ammonaps and by Fyrlklövern Scandinavia as triButyrate.
Sodium phenylbutyrate is used to treat urea cycle disorders.[1]
Structure and properties
The chemical name for sodium phenylbutyrate is 4-phenylbutyric acid, sodium salt. It consists of water-soluble off-white crystals.[2]
Uses
Medical uses
Phenylbutyrate is taken orally as a tablet or powder, and tastes salty. It treats urea cycle disorders, genetic diseases in which nitrogen waste builds up in the blood plasma as ammonia glutamine (hyperammonemia) due to deficiences in the enzymes carbamylphosphate synthetase, ornithine transcarbamylase, or argininosuccinic acid synthetase.[1][2] This causes mental retardation and early death.[2] Sodium phenylbutyrate metabolites allows the kidneys to excrete excess nitrogen in place of urea, and coupled with dialysis, amino acid supplements and a protein-restricted diet, children born with urea cycle disorders can now survive beyond 12 months.[2] Patients may need treatment for all their life.[2]
Adverse effects
Nearly 1/4 women may experience an adverse effect of amenorrhea or menstrual dysfunction.[2] Appetite loss is seen is 4% of patients. Body odor due to metabolization of pheylbutyrate affects 3% of patients, and 3% experience unpleasant tastes. Gastrointestinal symptoms and mostly mild indications of neurotoxicity are also seen in less than 2% of patients, among several others reported adverse effects.[2]
Research
Sodium phenylbutyrate is under investigation for the treatment of some sickle-cell disorders (Blood Products Plasma Expanders and Haemostatics) and for use as a potential differentiation-inducing agent in malignant glioma and acute myeloid leukaemia.[citation needed]
Phenylbutyrate has been associated with longer lifespans in Drosophila.[3]
University of Colorado researchers Dr. Curt Freed and Wenbo Zhou demonstrated that phenylbutyrate stops the progression of Parkinson's disease in mice by turning on a gene called DJ-1 that can protect dopaminergic neurons in the midbrain from dying. As of July 2011 they plan on testing phenylbutyrate for the treatment of Parkinson's disease in humans.[4]
Pharmacology
Phenylbutyrate is a prodrug. In the human body it is metabolized, mainly in the liver and kidneys by beta-oxidation, to phenylacetate. Phenylacetate conjugates with glutamine to phenylacetylglutamine, which is eliminated with the urine. It contains the same amount of nitrogen as urea, which makes it an alternative to urea for excreting nitrogen.[2]
A 5g tablet or powder of sodium phenylbutyrate taken by mouth can be detected in the blood within 15 minutes, and reaches peak concentration in the bloodstream within an hour. It is metabolized into phenylacetate within half an hour.[2]
References
- ^ a b Batshaw, M. L.; MacArthur, R. B.; Tuchman, M. (2001). "Alternative pathway therapy for urea cycle disorders: twenty years later". J. Pediatr. 138 (1 Suppl): S46–S54, discussion S54–S55. doi:10.1067/mpd.2001.111836. PMID 11148549.
- ^ a b c d e f g h i "Buphenyl". DailyMed. U.S. National Library of Medicine. September 2006. Retrieved 25 October 2013.
- ^ Kang, H. L.; Benzer, S.; Min, K. T. (2002). "Life extension in Drosophila by feeding a drug". Proc. Natl. Acad. Sci. U.S.A. 99 (2): 838–843. doi:10.1073/pnas.022631999. PMC 117392. PMID 11792861.
- ^ News Article