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
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