U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Uridine triacetate is used to treat an overdose of capecitabine or fluorouracil. In addition, it is used as a pyrimidine analog for uridine replacement indicated for the treatment of hereditary orotic aciduria. Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation. Uridine competitively inhibits cell damage and cell death caused by fluorouracil. Uridine can be used by essentially all cells to make uridine nucleotides, compensating for the genetic deficiency in synthesis in patients with hereditary orotic aciduria. When intracellular uridine nucleotides are restored into the normal range, overproduction of orotic acid is reduced by feedback inhibition, so that urinary excretion of orotic acid is also reduced. Adverse reactions occurring in >2% of patients receiving uridine triacetate included vomiting, nausea, and diarrhea. In vitro data showed that uridine triacetate was a weak substrate for P-glycoprotein. Due to the potential for high local (gut) concentrations of the drug after dosing, the interaction of uridine triacetate with orally administered P-gp substrate drugs cannot be ruled out.
Status:
Investigational
Source:
NCT02073838: Phase 2 Human clinical trial Completed Leukemia, Myeloid, Acute/genetics/metabolism
Source URL:

Class (Stereo):
CHEMICAL (ABSOLUTE)


Status:
Possibly Marketed Outside US

Class (Stereo):
CHEMICAL (ABSOLUTE)

Uridine 5'-triphosphate (UTP, INS316) is a naturally occurring agonist for P2Y(2) receptors on the apical surface of ciliated respiratory epithelium. INS316, being developed by Inspire Pharmaceuticals, is a short-acting, aerosolized uridine 5-triphosphate (UTP) solution used as a diagnostic aid for lung cancer. INS316 appears to improve sputum expectoration mediated through the P2Y2 receptor, a nucleotide receptor expressed in human airway epithelial cells and some other tissues. UTP binding to the P2Y2 receptor triggers signal transduction that leads to chloride ion secretion, thereby resulting in mucociliary clearance of airway. UTP stimulates salt and water transport and cilia beat frequency in human airway epithelium in vitro. Single, inhaled doses of UTP stimulate mucociliary clearance in conscious, intubated sheep and in patients with mild chronic bronchitis (smokers and former smokers), suggesting that UTP may be useful for obtaining deep-lung sputum specimens suitable for diagnostic purposes. A single dose of INS316 safely improves the ability of patients with mild chronic bronchitis to expectorate a deep-lung sputum specimen suitable for cytologic evaluation.
Uridine triacetate is used to treat an overdose of capecitabine or fluorouracil. In addition, it is used as a pyrimidine analog for uridine replacement indicated for the treatment of hereditary orotic aciduria. Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation. Uridine competitively inhibits cell damage and cell death caused by fluorouracil. Uridine can be used by essentially all cells to make uridine nucleotides, compensating for the genetic deficiency in synthesis in patients with hereditary orotic aciduria. When intracellular uridine nucleotides are restored into the normal range, overproduction of orotic acid is reduced by feedback inhibition, so that urinary excretion of orotic acid is also reduced. Adverse reactions occurring in >2% of patients receiving uridine triacetate included vomiting, nausea, and diarrhea. In vitro data showed that uridine triacetate was a weak substrate for P-glycoprotein. Due to the potential for high local (gut) concentrations of the drug after dosing, the interaction of uridine triacetate with orally administered P-gp substrate drugs cannot be ruled out.