About 4-PBA (Sodium 4-Phenylbutyrate)
By Christine M. Vocke and Sharon F. Terry, PXE International
Q1. What is Sodium 4-Phenylbutyrate (4-PBA)?
A1. Sodium 4-Phenylbutyrate (4-PBA) is a prodrug of phenylacetate, which is a fatty acid (building blocks of the fat in our bodies and in the food we eat). Sodium Phenylbutyrate is an orphan drug used to treat urea cycle disorders, because its metabolites offer an alternative pathway to the urea cycle to allow excretion of excess nitrogen. Phenylbutyrate and its metabolites (substance produced during digestion or other bodily chemical processes) have been shown to increase fetal hemoglobin production in patients with thalassemia and sickle cell disease. Data also indicate that they enhance cytotoxicity (the quality of being toxic to cells) of chemo agents such as doxorubicin and cisplatin (chemotherapy drug), and exert antibacterial effects against Helicobacter pylori (stomach-associated bacteria) in vitro (studies performed outside the cell’s normal biological context).
Sodium phenylbutyrate is converted to a substance in the body that helps the kidneys eliminate waste substances from the body. These waste substances can produce ammonia, which is toxic if it builds up in your blood. Sodium phenylbutyrate is used to treat urea cycle disorders in people who lack certain liver enzymes needed to properly eliminate waste substances from the body. This medication helps prevent a build-up of ammonia in the blood.
Mechanism of Action
In urea cycle disorders, phenylacetate reduces or normalizes serum ammonium and glutamate levels. Phenylbutyrate and its metabolites have been shown to increase fetal hemoglobin production in patients with thalassemia and sickle cell disease. In vitro studies suggest that phenylbutyrate causes cancer cell cytostasis (inhibition of cell growth and multiplication), differentiation (changes a cell's size, shape, membrane potential, metabolic activity, and responsiveness to signals), and apoptosis (cell death). Phenylbutyrate also increases the sensitivity of head and neck cancer cells to cisplatin. Animal studies indicate that phenylbutyrate, when combined with 13-cis retinoic acid (an anti-cancer drug), prevents angiogenesis (new blood vessels form from pre-existing vessels) and causes apoptosis of prostate cancer cells.
Q2. Are there any side effects or adverse reactions to taking sodium phenylbutyrate?
A2. Common symptoms include: fatigue, dyspepsia, nausea, vomiting, body odor, anorexia, menstrual cycle irregularities, and amenorrhea. Reported symptoms include: hypocalcemia, edema (possibly related to sodium content), skin rash.
Rare symptoms: liver toxicity (elevations in AST, ALT, bilirubin, and alk phos, which are sensitive indicators of liver damage or injury), renal tubular acidosis (accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine).
It is a FDA pregnancy category C drug, meaning it is not known whether sodium phenylbutyrate is harmful to an unborn baby. It is not known whether sodium phenylbutyrate passes into breast milk or if it could harm a nursing baby. It is not recommended that it be used in a child under 44 pounds.
Q3. What needs to be done to test whether this would be a useful drug in treating pseudoxanthoma elasticum (PXE)?
A3. More work on animal models must be done. So far, researchers have shown that it might reduce mineralization in individuals with certain missence mutations.
 Memorial Sloan Kettering Cancer Center. Phenylbutyrate. Retrieved 15 October 2014 from: http://www.mskcc.org/cancer-care/herb/phenylbutyrate
 United States Food and Drug Administration. Drugs at the FDA: Sodium Phenylbutyrate. Retrieved 15 October 2014 from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020572s016,020573s015lbl.pdf
Last updated May 18th, 2016