4-phenylbutyrate
4-phenylbutyrate Uses, Dosage, Side Effects, Food Interaction and all others data.
A monocarboxylic acid the structure of which is that of butyric acid substituted with a phenyl group at C-4. It is a histone deacetylase inhibitor that displays anticancer activity. It inhibits cell proliferation, invasion and migration and induces apoptosis in glioma cells. It also inhibits protein isoprenylation, depletes plasma glutamine, increases production of foetal haemoglobin through transcriptional activation of the γ-globin gene and affects hPPARγ activation.
Decreases elevated plasma ammonia glutamine levels
Trade Name | 4-phenylbutyrate |
Generic | Phenylbutyric acid |
Phenylbutyric acid Other Names | 4-phenylbutyrate, 4-phenylbutyric acid, Benzenebutyric acid, Phenylbutyrate, ω-Phenylbutanoic acid, ω-phenylbutyric acid |
Type | |
Formula | C10H12O2 |
Weight | Average: 164.2011 Monoisotopic: 164.083729628 |
Protein binding | phenylbutyrate and Phenylacetate concentrations in the plasma were determined by high-performance liquid chromatography. Both drugs exhibited concentration-dependent binding. Results showed sodium phenylacetate to have a higher free fraction than sodium phenylbutyrate at corresponding concentrations (> 0.442 +/- 0.008 and > 0.188 +/- 0.001, respectively). Both have high free fractions in plasma. |
Groups | Approved, Investigational |
Therapeutic Class | |
Manufacturer | |
Available Country | |
Last Updated: | September 19, 2023 at 7:00 am |
Uses
4-phenylbutyrate is an agent indicated for the adjunctive therapy for the management of chronic urea cycle disorders due to deficiencies in specific enzymes, including the neonatal-onset deficiency and late-onset disease with a history of hyperammonemic encephalopathy.
Adjunctive therapy for the management of chronic urea cycle disorders due to deficiencies in carbamylphosphate (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase. it is indicated in all neonatal- onset efficiency presenting within the first 28 days of life. Also indicated in patients with late-onset, presenting after the first month of life with a history of hyperammonemic encephalopathy.
4-phenylbutyrate is also used to associated treatment for these conditions: Deficiencies in enzymes of the urea cycle
How 4-phenylbutyrate works
Sodium phenylbutyrate is a pro-drug that is metabolized to the active compound phenylacetate. Phenylacetate conjuages with glutamine via acetylation reaction to form the product phenylacetylglutamine, which is excreted by the kidneys. This provides an alternative mechanism for waste nitrogen excretion.
Toxicity
Clinical adverse reaction: In females who were menstruating, 23% reported amenorrhea or menstrual dysfunction. In all patients, 4% reported a decreased appetite, and body odor issues, and 3% of patients report a taste aversion. Other adverse events that occurred in less than 2% of patients were abdominal pain, gastritis, nausea and vomiting, constipation, rectal bleeding, peptic ulcer disease, pancreatitis, aplastic anemia, ecchymosis, arrhythmia, edema, renal tubular acidosis, depressions, skin rash, headache, syncope, and weight gain occurring in at least one patient. Laboratory adverse events: Changes to baseline laboratory values were also observed. The events include: acidosis (14%), alkalosis and hyperchloremia (7%), hypophosphatemia (6%), hyperuricemia and hyperphosphatemia (2%), hypernatremia and hypokalemia (1%), hypoalbuminemia (11%), decreased total protein (3%), increase alkaline phosphate (6%), increased liver transaminases (4%), hyperbilirubinemia (1%), anemia (9%), leukopenia and leukocytosis (4%), thrombocytopenia (3%) and thrombocytosis (1%).
Food Interaction
- Take with food.
Volume of Distribution
The volume of distribution of phenylbutyrate is 0.2 l/kg.
Elimination Route
Under fasting condition the Cmax of a single orally ingested 5g tablet and 5g powder after 1 hour are respectively 218mcg/ml and 195mcg/ml. The effect of food on phenylbutyrate absorption is still unknown.
Half Life
For sodium phenylbutyrate the half life is 0.77 hours. For phenylacetate the half life is 1.15 hours.
Clearance
Within 24 hours 80-100% of the administered dose in eliminated in the urine as pheylacetylglutamine.
Elimination Route
The major route of elimination is the kidneys as phenylacetylglutamine.
Innovators Monograph
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