4-Phenylbutyric acid

164.2

164.20

638180

217-341-8

7WY7YBI87E

295

TSCA listed

DTXSID2037631

White to slightly yellow

29163900

2.42 (LogP)|2.42

1.0326 (rough estimate)

49-51 °C(lit.)

165 °C10 mm Hg(lit.)

1.5405 (estimate)

5.3 g/L at 40 ºC

4.76(at 25℃)

Sealed in dry,Room Temperature

3

Xi

22-24/25-36-26

36/37/38

|Warning|H315 (83.33%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 12 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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%).

While the urea cycle disorders are caused by deficiencies of hepatic enzymes responsible for the elimination of nitrogen, patients generally present with hyperammonemia without other features or biochemical evidence of hepatic injury. Thus, serum aminotransferase, alkaline phosphatase and bilirubin levels are generally normal or only mildly elevated. Newborns presenting with hyperammonemia may have hepatomegaly but other, non-urea cycle, liver function is normal as is hepatic histology. Phenylbutyrate can help to lower ammonia levels acutely and manage to keep them in the normal or near normal range, but generally does not affect other liver functions. In open label studies, a small proportion of patients (particularly with ornithine transcarbamylase [OTC] deficiency) have had ALT or AST elevations, but these have generally been attributed to the underlying condition or its complications. Phenylbutyrate has not been linked to instances of clinically apparent liver injury with jaundice.

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.

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.|FDA Label

Phenylbutyrate and sodium benzoate are orphan drugs approved for the treatment of hyperammonemia in patients with urea cycle disorders, a series of at least 8 rare genetic enzyme deficiencies. The urea cycle is the major pathway of elimination of excess nitrogen including ammonia, and absence of one of the urea cycle enzymes often causes elevations in serum ammonia which can be severe, life-threatening and result in permanent neurologic damage and cognitive deficiencies. Both phenylbutyrate and sodium benzoate act by promoting an alternative pathway of nitrogen elimination. Neither phenylbutyrate nor sodium benzoate have been linked to cases of liver injury either in the form of serum enzyme elevations during therapy or clinically apparent acute liver injury.

Urea Cycle Disorder Agents

Decreases elevated plasma ammonia glutamine levels

Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)

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.|The major route of elimination is the kidneys as phenylacetylglutamine.|The volume of distribution of phenylbutyrate is 0.2 l/kg.|Within 24 hours 80-100% of the administered dose in eliminated in the urine as pheylacetylglutamine.

The overall disposition of sodium phenylbutyrate and its metabolites has not been characterized fully. However, the drug is known to be metabolized to phenylacetate and subsequently to phenylacetylglutamine. Metabolism of phenylbutyrate occurs mainly in liver and kidney.

For sodium phenylbutyrate the half life is 0.77 hours. For phenylacetate the half life is 1.15 hours.

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.

4-phenylbutyrate

Benzenebutanoic acid: ACTIVE