Details
Stereochemistry | ACHIRAL |
Molecular Formula | C10H12O2 |
Molecular Weight | 164.2011 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)CCCC1=CC=CC=C1
InChI
InChIKey=OBKXEAXTFZPCHS-UHFFFAOYSA-N
InChI=1S/C10H12O2/c11-10(12)8-4-7-9-5-2-1-3-6-9/h1-3,5-6H,4,7-8H2,(H,11,12)
Molecular Formula | C10H12O2 |
Molecular Weight | 164.2011 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Sodium phenylbutyrate is a salt of an aromatic fatty acid. The compound is used to treat urea cycle disorders, because its metabolites offer an alternative pathway to the urea cycle to allow excretion of excess nitrogen. Sodium phenylbutyrate is also a histone deacetylase inhibitor and chemical chaperone, leading respectively to research into its use as an anti-cancer agent and in protein misfolding diseases such as cystic fibrosis. It is used as 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. Sodium phenylbutyrate is a pro-drug and is rapidly metabolized to phenylacetate. Phenylacetate is a metabolically active compound that conjugates with glutamine via acetylation to form phenylacetylglutamine. The kidneys then excrete Phenylacetylglutamine. PBA (phenylbutyric acid) is absorbed from the intestine and converted by way of β-oxidation to the active moiety, phenylacetic acid (PAA). PAA is conjugated with glutamine in the liver and kidney by way of N-acyl coenzyme A-l-glutamine N-acyltransferase to form phenylacetylglutamine (PAGN). Like urea, PAGN incorporates two waste nitrogens and is excreted in the urine. On a molar basis, it is comparable to urea (each containing two moles of nitrogen). Therefore, phenylacetylglutamine provides an alternate vehicle for waste nitrogen excretion.
CNS Activity
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000219/WC500024748.pdf
Curator's Comment: It was argued that high concentrations are unlikely during therapeutic use of sodium phenylbutyrate (PB) because of poor transfer across the adult blood-brain barrier. The implications of these findings with respect to human foetal brain are unknown.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: GO:0007050 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19024104 |
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6.34 µM [Ki] | |||
Target ID: CHEMBL2366039 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20512995 |
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Target ID: Nitrogen |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | BUPHENYL Approved UseBUPHENYL® is indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). It is indicated in all patients with neonatal-onset deficiency (complete enzymatic deficiency, presenting within the first 28 days of life). It is also indicated in patients with late-onset disease (partial enzymatic deficiency, presenting after the first month of life) who have a history of hyperammonemic encephalopathy. It is important that the diagnosis be made early and treatment initiated immediately to improve survival. Any episode of acute hyperammonemia should be treated as a lifethreatening emergency. Launch Date1996 |
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Palliative | BUPHENYL Approved UseBUPHENYL® is indicated as adjunctive therapy in the chronic management of patients with urea cycle disorders involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). It is indicated in all patients with neonatal-onset deficiency (complete enzymatic deficiency, presenting within the first 28 days of life). It is also indicated in patients with late-onset disease (partial enzymatic deficiency, presenting after the first month of life) who have a history of hyperammonemic encephalopathy. It is important that the diagnosis be made early and treatment initiated immediately to improve survival. Any episode of acute hyperammonemia should be treated as a lifethreatening emergency. Launch Date1996 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
949.9 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
18 g 1 times / day multiple, oral dose: 18 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
1679.8 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
27 g 1 times / day multiple, oral dose: 27 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
1878.3 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
36 g 1 times / day multiple, oral dose: 36 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
1669.4 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
45 g 1 times / day multiple, oral dose: 45 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
457.9 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
9 g 1 times / day multiple, oral dose: 9 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
218 μg/mL |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2170.6 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
18 g 1 times / day multiple, oral dose: 18 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
3778.6 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
27 g 1 times / day multiple, oral dose: 27 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
4687.4 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
36 g 1 times / day multiple, oral dose: 36 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
4941.4 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
45 g 1 times / day multiple, oral dose: 45 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
925.5 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
9 g 1 times / day multiple, oral dose: 9 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.61 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
18 g 1 times / day multiple, oral dose: 18 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
0.58 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
27 g 1 times / day multiple, oral dose: 27 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
0.94 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
36 g 1 times / day multiple, oral dose: 36 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
1.16 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
45 g 1 times / day multiple, oral dose: 45 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
0.76 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11489804 |
9 g 1 times / day multiple, oral dose: 9 g route of administration: Oral experiment type: MULTIPLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
0.77 h |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.3% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8946671 |
unknown, unknown |
SODIUM PHENYLBUTYRATE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
18 g 1 times / day steady, oral Dose: 18 g, 1 times / day Route: oral Route: steady Dose: 18 g, 1 times / day Sources: |
unhealthy, 31-73 years n = 11 Health Status: unhealthy Condition: Huntington’s Disease Age Group: 31-73 years Sex: M+F Population Size: 11 Sources: |
DLT: Nausea, Vomiting... Dose limiting toxicities: Nausea (grade 3, 2 patients) Sources: Vomiting (grade 3, 1 patient) Gait instability (grade 3, 2 patients) Lightheadedness (grade 3, 2 patients) Confusion (grade 3, 1 patient) |
15 g 1 times / day steady, oral MTD Dose: 15 g, 1 times / day Route: oral Route: steady Dose: 15 g, 1 times / day Sources: |
unhealthy, 38-61 years n = 4 Health Status: unhealthy Condition: Huntington’s Disease Age Group: 38-61 years Sex: M+F Population Size: 4 Sources: |
Other AEs: Nausea, Gait instability... Other AEs: Nausea (grade 1, 2 patients) Sources: Gait instability (grade 1, 1 patient) Syncope vasovagal (grade 2, 2 patients) Diarrhea (grade 1, 1 patient) |
27 g 1 times / day steady, oral MTD Dose: 27 g, 1 times / day Route: oral Route: steady Dose: 27 g, 1 times / day Sources: |
unhealthy, 51.4 years (range: 29.7–71.1 years) n = 7 Health Status: unhealthy Condition: recurrent malignant gliomas Age Group: 51.4 years (range: 29.7–71.1 years) Sex: M+F Population Size: 7 Sources: |
DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3, 1 patient) Sources: |
36 g 1 times / day steady, oral Dose: 36 g, 1 times / day Route: oral Route: steady Dose: 36 g, 1 times / day Sources: |
unhealthy, 51.4 years (range: 29.7–71.1 years) n = 4 Health Status: unhealthy Condition: recurrent malignant gliomas Age Group: 51.4 years (range: 29.7–71.1 years) Sex: M+F Population Size: 4 Sources: |
DLT: Fatigue, Somnolence... Dose limiting toxicities: Fatigue (grade 3, 2 patients) Sources: Somnolence (grade 3, 2 patients) Anemia (grade 3, 1 patient) Neutropenia (grade 3, 1 patient) |
45 g single, intravenous Highest studied dose Dose: 45 g Route: intravenous Route: single Dose: 45 g Sources: |
unhealthy, 57 years (range: 26–75 years) n = 4 Health Status: unhealthy Age Group: 57 years (range: 26–75 years) Sex: M+F Population Size: 4 Sources: |
|
45 g 1 times / day steady, oral Highest studied dose Dose: 45 g, 1 times / day Route: oral Route: steady Dose: 45 g, 1 times / day Sources: |
unhealthy, 57 years (range: 26–75 years) n = 4 Health Status: unhealthy Age Group: 57 years (range: 26–75 years) Sex: M+F Population Size: 4 Sources: |
DLT: Fatigue, Central nervous system toxicity... Other AEs: Nausea, Vomiting... Dose limiting toxicities: Fatigue (grade 3-4, 1 patient) Other AEs:Central nervous system toxicity (grade 3-4, 1 patient) Nausea (grade 3-4, 1 patient) Sources: Vomiting (grade 3-4, 1 patient) Edema (grade 3-4, 1 patient) |
36 g 1 times / day steady, oral Dose: 36 g, 1 times / day Route: oral Route: steady Dose: 36 g, 1 times / day Sources: |
unhealthy, 57 years (range: 26–75 years) n = 7 Health Status: unhealthy Age Group: 57 years (range: 26–75 years) Sex: M+F Population Size: 7 Sources: |
DLT: Nausea, Vomiting... Dose limiting toxicities: Nausea (grade 3-4, 1 patient) Sources: Vomiting (grade 3-4, 1 patient) Hypocalcemia (grade 3-4, 1 patient) |
150 mg/kg 3 times / day steady, oral MTD Dose: 150 mg/kg, 3 times / day Route: oral Route: steady Dose: 150 mg/kg, 3 times / day Sources: |
unhealthy, 57 years(range: 25–71 years) n = 3 Health Status: unhealthy Age Group: 57 years(range: 25–71 years) Sex: M+F Population Size: 3 Sources: |
DLT: Fatigue... Other AEs: Anemia, Light-headed... Dose limiting toxicities: Fatigue (grade 2, 2 patients) Other AEs:Anemia (grade 3, 1 patient) Sources: Light-headed (grade 2, 2 patients) Edema (grade 2, 2 patients) Nausea (grade 2, 1 patient) Vomiting (grade 2, 1 patient) Constipation (grade 1, 2 patients) Fever (grade 1, 1 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Confusion | grade 3, 1 patient DLT |
18 g 1 times / day steady, oral Dose: 18 g, 1 times / day Route: oral Route: steady Dose: 18 g, 1 times / day Sources: |
unhealthy, 31-73 years n = 11 Health Status: unhealthy Condition: Huntington’s Disease Age Group: 31-73 years Sex: M+F Population Size: 11 Sources: |
Vomiting | grade 3, 1 patient DLT |
18 g 1 times / day steady, oral Dose: 18 g, 1 times / day Route: oral Route: steady Dose: 18 g, 1 times / day Sources: |
unhealthy, 31-73 years n = 11 Health Status: unhealthy Condition: Huntington’s Disease Age Group: 31-73 years Sex: M+F Population Size: 11 Sources: |
Gait instability | grade 3, 2 patients DLT |
18 g 1 times / day steady, oral Dose: 18 g, 1 times / day Route: oral Route: steady Dose: 18 g, 1 times / day Sources: |
unhealthy, 31-73 years n = 11 Health Status: unhealthy Condition: Huntington’s Disease Age Group: 31-73 years Sex: M+F Population Size: 11 Sources: |
Lightheadedness | grade 3, 2 patients DLT |
18 g 1 times / day steady, oral Dose: 18 g, 1 times / day Route: oral Route: steady Dose: 18 g, 1 times / day Sources: |
unhealthy, 31-73 years n = 11 Health Status: unhealthy Condition: Huntington’s Disease Age Group: 31-73 years Sex: M+F Population Size: 11 Sources: |
Nausea | grade 3, 2 patients DLT |
18 g 1 times / day steady, oral Dose: 18 g, 1 times / day Route: oral Route: steady Dose: 18 g, 1 times / day Sources: |
unhealthy, 31-73 years n = 11 Health Status: unhealthy Condition: Huntington’s Disease Age Group: 31-73 years Sex: M+F Population Size: 11 Sources: |
Diarrhea | grade 1, 1 patient | 15 g 1 times / day steady, oral MTD Dose: 15 g, 1 times / day Route: oral Route: steady Dose: 15 g, 1 times / day Sources: |
unhealthy, 38-61 years n = 4 Health Status: unhealthy Condition: Huntington’s Disease Age Group: 38-61 years Sex: M+F Population Size: 4 Sources: |
Gait instability | grade 1, 1 patient | 15 g 1 times / day steady, oral MTD Dose: 15 g, 1 times / day Route: oral Route: steady Dose: 15 g, 1 times / day Sources: |
unhealthy, 38-61 years n = 4 Health Status: unhealthy Condition: Huntington’s Disease Age Group: 38-61 years Sex: M+F Population Size: 4 Sources: |
Nausea | grade 1, 2 patients | 15 g 1 times / day steady, oral MTD Dose: 15 g, 1 times / day Route: oral Route: steady Dose: 15 g, 1 times / day Sources: |
unhealthy, 38-61 years n = 4 Health Status: unhealthy Condition: Huntington’s Disease Age Group: 38-61 years Sex: M+F Population Size: 4 Sources: |
Syncope vasovagal | grade 2, 2 patients | 15 g 1 times / day steady, oral MTD Dose: 15 g, 1 times / day Route: oral Route: steady Dose: 15 g, 1 times / day Sources: |
unhealthy, 38-61 years n = 4 Health Status: unhealthy Condition: Huntington’s Disease Age Group: 38-61 years Sex: M+F Population Size: 4 Sources: |
Fatigue | grade 3, 1 patient DLT |
27 g 1 times / day steady, oral MTD Dose: 27 g, 1 times / day Route: oral Route: steady Dose: 27 g, 1 times / day Sources: |
unhealthy, 51.4 years (range: 29.7–71.1 years) n = 7 Health Status: unhealthy Condition: recurrent malignant gliomas Age Group: 51.4 years (range: 29.7–71.1 years) Sex: M+F Population Size: 7 Sources: |
Anemia | grade 3, 1 patient DLT |
36 g 1 times / day steady, oral Dose: 36 g, 1 times / day Route: oral Route: steady Dose: 36 g, 1 times / day Sources: |
unhealthy, 51.4 years (range: 29.7–71.1 years) n = 4 Health Status: unhealthy Condition: recurrent malignant gliomas Age Group: 51.4 years (range: 29.7–71.1 years) Sex: M+F Population Size: 4 Sources: |
Neutropenia | grade 3, 1 patient DLT |
36 g 1 times / day steady, oral Dose: 36 g, 1 times / day Route: oral Route: steady Dose: 36 g, 1 times / day Sources: |
unhealthy, 51.4 years (range: 29.7–71.1 years) n = 4 Health Status: unhealthy Condition: recurrent malignant gliomas Age Group: 51.4 years (range: 29.7–71.1 years) Sex: M+F Population Size: 4 Sources: |
Fatigue | grade 3, 2 patients DLT |
36 g 1 times / day steady, oral Dose: 36 g, 1 times / day Route: oral Route: steady Dose: 36 g, 1 times / day Sources: |
unhealthy, 51.4 years (range: 29.7–71.1 years) n = 4 Health Status: unhealthy Condition: recurrent malignant gliomas Age Group: 51.4 years (range: 29.7–71.1 years) Sex: M+F Population Size: 4 Sources: |
Somnolence | grade 3, 2 patients DLT |
36 g 1 times / day steady, oral Dose: 36 g, 1 times / day Route: oral Route: steady Dose: 36 g, 1 times / day Sources: |
unhealthy, 51.4 years (range: 29.7–71.1 years) n = 4 Health Status: unhealthy Condition: recurrent malignant gliomas Age Group: 51.4 years (range: 29.7–71.1 years) Sex: M+F Population Size: 4 Sources: |
Edema | grade 3-4, 1 patient | 45 g 1 times / day steady, oral Highest studied dose Dose: 45 g, 1 times / day Route: oral Route: steady Dose: 45 g, 1 times / day Sources: |
unhealthy, 57 years (range: 26–75 years) n = 4 Health Status: unhealthy Age Group: 57 years (range: 26–75 years) Sex: M+F Population Size: 4 Sources: |
Nausea | grade 3-4, 1 patient | 45 g 1 times / day steady, oral Highest studied dose Dose: 45 g, 1 times / day Route: oral Route: steady Dose: 45 g, 1 times / day Sources: |
unhealthy, 57 years (range: 26–75 years) n = 4 Health Status: unhealthy Age Group: 57 years (range: 26–75 years) Sex: M+F Population Size: 4 Sources: |
Vomiting | grade 3-4, 1 patient | 45 g 1 times / day steady, oral Highest studied dose Dose: 45 g, 1 times / day Route: oral Route: steady Dose: 45 g, 1 times / day Sources: |
unhealthy, 57 years (range: 26–75 years) n = 4 Health Status: unhealthy Age Group: 57 years (range: 26–75 years) Sex: M+F Population Size: 4 Sources: |
Central nervous system toxicity | grade 3-4, 1 patient DLT, Disc. AE |
45 g 1 times / day steady, oral Highest studied dose Dose: 45 g, 1 times / day Route: oral Route: steady Dose: 45 g, 1 times / day Sources: |
unhealthy, 57 years (range: 26–75 years) n = 4 Health Status: unhealthy Age Group: 57 years (range: 26–75 years) Sex: M+F Population Size: 4 Sources: |
Fatigue | grade 3-4, 1 patient DLT, Disc. AE |
45 g 1 times / day steady, oral Highest studied dose Dose: 45 g, 1 times / day Route: oral Route: steady Dose: 45 g, 1 times / day Sources: |
unhealthy, 57 years (range: 26–75 years) n = 4 Health Status: unhealthy Age Group: 57 years (range: 26–75 years) Sex: M+F Population Size: 4 Sources: |
Hypocalcemia | grade 3-4, 1 patient DLT |
36 g 1 times / day steady, oral Dose: 36 g, 1 times / day Route: oral Route: steady Dose: 36 g, 1 times / day Sources: |
unhealthy, 57 years (range: 26–75 years) n = 7 Health Status: unhealthy Age Group: 57 years (range: 26–75 years) Sex: M+F Population Size: 7 Sources: |
Nausea | grade 3-4, 1 patient DLT |
36 g 1 times / day steady, oral Dose: 36 g, 1 times / day Route: oral Route: steady Dose: 36 g, 1 times / day Sources: |
unhealthy, 57 years (range: 26–75 years) n = 7 Health Status: unhealthy Age Group: 57 years (range: 26–75 years) Sex: M+F Population Size: 7 Sources: |
Vomiting | grade 3-4, 1 patient DLT |
36 g 1 times / day steady, oral Dose: 36 g, 1 times / day Route: oral Route: steady Dose: 36 g, 1 times / day Sources: |
unhealthy, 57 years (range: 26–75 years) n = 7 Health Status: unhealthy Age Group: 57 years (range: 26–75 years) Sex: M+F Population Size: 7 Sources: |
Fever | grade 1, 1 patient | 150 mg/kg 3 times / day steady, oral MTD Dose: 150 mg/kg, 3 times / day Route: oral Route: steady Dose: 150 mg/kg, 3 times / day Sources: |
unhealthy, 57 years(range: 25–71 years) n = 3 Health Status: unhealthy Age Group: 57 years(range: 25–71 years) Sex: M+F Population Size: 3 Sources: |
Constipation | grade 1, 2 patients | 150 mg/kg 3 times / day steady, oral MTD Dose: 150 mg/kg, 3 times / day Route: oral Route: steady Dose: 150 mg/kg, 3 times / day Sources: |
unhealthy, 57 years(range: 25–71 years) n = 3 Health Status: unhealthy Age Group: 57 years(range: 25–71 years) Sex: M+F Population Size: 3 Sources: |
Nausea | grade 2, 1 patient | 150 mg/kg 3 times / day steady, oral MTD Dose: 150 mg/kg, 3 times / day Route: oral Route: steady Dose: 150 mg/kg, 3 times / day Sources: |
unhealthy, 57 years(range: 25–71 years) n = 3 Health Status: unhealthy Age Group: 57 years(range: 25–71 years) Sex: M+F Population Size: 3 Sources: |
Vomiting | grade 2, 1 patient | 150 mg/kg 3 times / day steady, oral MTD Dose: 150 mg/kg, 3 times / day Route: oral Route: steady Dose: 150 mg/kg, 3 times / day Sources: |
unhealthy, 57 years(range: 25–71 years) n = 3 Health Status: unhealthy Age Group: 57 years(range: 25–71 years) Sex: M+F Population Size: 3 Sources: |
Edema | grade 2, 2 patients | 150 mg/kg 3 times / day steady, oral MTD Dose: 150 mg/kg, 3 times / day Route: oral Route: steady Dose: 150 mg/kg, 3 times / day Sources: |
unhealthy, 57 years(range: 25–71 years) n = 3 Health Status: unhealthy Age Group: 57 years(range: 25–71 years) Sex: M+F Population Size: 3 Sources: |
Light-headed | grade 2, 2 patients | 150 mg/kg 3 times / day steady, oral MTD Dose: 150 mg/kg, 3 times / day Route: oral Route: steady Dose: 150 mg/kg, 3 times / day Sources: |
unhealthy, 57 years(range: 25–71 years) n = 3 Health Status: unhealthy Age Group: 57 years(range: 25–71 years) Sex: M+F Population Size: 3 Sources: |
Fatigue | grade 2, 2 patients DLT, Disc. AE |
150 mg/kg 3 times / day steady, oral MTD Dose: 150 mg/kg, 3 times / day Route: oral Route: steady Dose: 150 mg/kg, 3 times / day Sources: |
unhealthy, 57 years(range: 25–71 years) n = 3 Health Status: unhealthy Age Group: 57 years(range: 25–71 years) Sex: M+F Population Size: 3 Sources: |
Anemia | grade 3, 1 patient | 150 mg/kg 3 times / day steady, oral MTD Dose: 150 mg/kg, 3 times / day Route: oral Route: steady Dose: 150 mg/kg, 3 times / day Sources: |
unhealthy, 57 years(range: 25–71 years) n = 3 Health Status: unhealthy Age Group: 57 years(range: 25–71 years) Sex: M+F Population Size: 3 Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
Pharmacology and safety of glycerol phenylbutyrate in healthy adults and adults with cirrhosis. | 2010 Jun |
|
Developing a new formulation of sodium phenylbutyrate. | 2012 Dec |
|
Sodium phenylbutyrate reverses lysosomal dysfunction and decreases amyloid-β42 in an in vitro-model of inclusion-body myositis. | 2014 May |
|
2017 Apr |
Patents
Sample Use Guides
Tablets is indicated for children weighing more than 20 kg and for adults. The usual total daily dose of Tablets and Powder for patients with urea cycle disorders is 450–600 mg/kg/day in patients weighing less than 20 kg, or 9.9–13.0 g/m2/day in larger patients. The tablets and powder are to be taken in equally divided amounts with each meal or feeding (i.e., three to six times per day). Powder is indicated for oral use (via mouth, gastrostomy, or nasogastric tube) only.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24472798
Curator's Comment: Sodium phenylbutyrate (NaPB) treatment reverses lysosomal dysfunction in an in vitro model of inclusion-body myositis, involving cultured human muscle fibers. NaPB treatment improved lysosomal activity, decreased Aβ42 and its oligomers, decreased γ-secretase activity, and virtually prevented muscle-fiber vacuolization
Unknown
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 16:37:56 GMT 2023
by
admin
on
Fri Dec 15 16:37:56 GMT 2023
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Record UNII |
7WY7YBI87E
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Record Status |
Validated (UNII)
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Record Version |
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-
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Systematic Name | English | ||
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FDA ORPHAN DRUG |
126199
Created by
admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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NDF-RT |
N0000175806
Created by
admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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NDF-RT |
N0000175807
Created by
admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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NCI_THESAURUS |
C1946
Created by
admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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DTXSID2037631
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8480
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DB06819
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81647
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100000153321
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C63699
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admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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C075773
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admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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295
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admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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7WY7YBI87E
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admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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41500
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admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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217-341-8
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admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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1546447
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admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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4775
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admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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1821-12-1
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admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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7WY7YBI87E
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admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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SUB127264
Created by
admin on Fri Dec 15 16:37:56 GMT 2023 , Edited by admin on Fri Dec 15 16:37:56 GMT 2023
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Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT |
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
MAJOR
URINE
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METABOLITE ACTIVE -> PRODRUG |
The active molecule that combines with glutamine (an amino acid with two nitrogen molecules) to form phenylacetylglutamine which is rapidly excreted by the kidneys and does not require metabolism via the urea cycle. Phenylbutyrate thus provides an “ammonia sink”, an alternative pathway for excretion of excess nitrogen and ammonia. The active metabolite phenylacetate is also effective therapeutically, but has a disagreeable odor and taste that affect compliance and acceptability.
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PRODRUG -> METABOLITE ACTIVE |
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METABOLITE -> PARENT |
EXCRETED IN URINE REMOVES AMMONIA FROM BODY
URINE
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METABOLITE -> PARENT |
Formed in the liver and excreted in the urine responsible for the reduction of ammonia in the blood.
MAJOR
URINE
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ACTIVE MOIETY |
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