Fenylbutyrát

Sodium 4-phenylbutyrate + ciglitizone

• Results in enhanced growth arrest of cancer cells
• Sodium phenylbutyrate; 0-5 mM
• Inhibits ASFV infection in a dose-dependent manner.
• Inhibits the ASFV late protein synthesis
• Disrupts the virus-induced H3K9/K14 hypoacetylation status

Sodium 4-phenylbutyrate + Enrofloxacin

• Synergistically to abolish ASFV replication
• Addition of Bafilomycin A1 results in accumulation of LC3II
• Benzenebutyric acid (4-PBA) substantially reduces this accumulation
• LPS decreases the level of p62, whereas Benzenebutyric acid reverses this decrease upon LPS stimulation for 48 h

Phenylbutyrate

• Prodrug metabolized to phenylacetate
• Active molecule that "combines with glutamine" (has two nitrogen molecules)
• To form phenylacetylglutamine
• Rapidly excreted by the kidneys
• Does not require metabolism via the urea cycle
• Phenylbutyrate = “ammonia sink”
• Alternative pathway for excretion of excess nitrogen and ammonia
• Za mne tedy přesně řečeno ev. prohlubuje případnou proteinovou deficienci tím, že snižuje hladinu glutaminu v krvi. Tedy brání vzniku budoucím molekulám dalšího amoniaku.
• Phenylbutyrate is odorless but does have a bitter, salty taste
• Must be given in high doses
• Often as 3 to 12 tablets three times daily

Phenylacetate

• Active metabolite therapeutically
• Disagreeable odor and taste

• Orphan drug approval for this indication in 1996
• In tablets of 500 mg and as a powder for oral solution under the brand name Buphenyl
• In general in the range of 5 to 20 grams daily given in three equally divided doses with meals.
• Phenylbutyrate is administered in conjunction with
• Low protein diet,
• Often combined with sodium benzoate (another ammonia “sink”)
• Essential amino acids (such as citrulline or arginine)
• Must be individualized
• Type of urea cycle disorder
• Clinical features.
• Bitter taste, loss of appetite, nausea, vomiting, diarrhea and edema.
• Rare side effects include fever and rash.
• Need to calculate dosages, overdosing can easily occur.
• Accidental use of higher than appropriate doses of phenylbutyrate
• Can result in severe metabolic side effects and death.

Glycerol-tri-phenylbutyrate

• Formulation that is both tasteless and odorless
• Low sodium content
• Can be given orally as a liquid in a small volume
• Approved for treatment of hyperammonemia due to urea cycle disorders in 2013
• Oral solution (1.1 g/mL) under the brand name Ravicti
• Typical dose is 5 to 12 g/m2 daily (~5-10 mL) in three divided doses with meals
• Common side effects of sodium phenylbutyrate such as
• Bitter taste, anorexia, nausea and vomiting are less with glycerol phenylbutyrate
• Care in calculation of the dose is critical
• Monitoring of ammonia and drug levels during treatment is recommended.
• www.ncbi.nlm.nih.gov/books/NBK547972/

RAVICTI

• Is for patients whose UCD cannot be managed by diet and supplements alone.
• RAVICTI must be used with a low-protein diet and, in some cases, with dietary supplements.
• RAVICTI has been proven to help manage ammonia levels for newborns, babies, children, and adults with urea cycle disorders
• Liquid medicine that is easy to take.
• It is odorless and nearly tasteless.
• Not used to treat extremely high levels of ammonia in the blood (hyperammonemic crisis) in people with UCDs.
• Not known if RAVICTI is safe and effective for the treatment of N-acetylglutamate synthase (NAGS) deficiency.
• Newborns, babies and toddlers may be prescribed up to 5 doses per day.
• Maximum approved daily dose of RAVICTI is 17.5 mL for both adults and children
• Adults and children age 2 years and up:
• In 3 equally divided doses, each rounded up to the nearest 0.5 mL
• Newborns and babies from birth up to 2 years:
• In 3 or more equally divided doses, each rounded up to the nearest 0.1 mL
• Infants who are breastfeeding,
• RAVICTI should be given just prior to breastfeeding