Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C9H12N2O6 |
| Molecular Weight | 244.2014 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N2C=CC(=O)NC2=O
InChI
InChIKey=DRTQHJPVMGBUCF-XVFCMESISA-N
InChI=1S/C9H12N2O6/c12-3-4-6(14)7(15)8(17-4)11-2-1-5(13)10-9(11)16/h1-2,4,6-8,12,14-15H,3H2,(H,10,13,16)/t4-,6-,7-,8-/m1/s1
DescriptionSources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208169Orig1s000Lbl.pdf | https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/27354750http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208169s000lbl.pdfCurator's Comment: description was created based on several sources, including:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf
http://www.rxlist.com/xuriden-drug.htm
https://www.drugs.com/mtm/uridine-triacetate.html
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208169Orig1s000Lbl.pdf | https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/27354750http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208169s000lbl.pdf
Curator's Comment: description was created based on several sources, including:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf
http://www.rxlist.com/xuriden-drug.htm
https://www.drugs.com/mtm/uridine-triacetate.html
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.
CNS Activity
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208169Orig1s000Lbl.pdf | https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/18540779https://www.ncbi.nlm.nih.gov/pubmed/16769123
Curator's Comment: Uridine triacetate is CNS penetrant and active.
Uridine triacetate is an acetylated prodrug of uridine. Circulating uridine is taken up into mammalian cells via specific nucleoside transporters, and also crosses the blood-brain barrier.
Uridine triacetate treatment may decrease symptoms of depression.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: GO:0008219 |
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Target ID: CHEMBL3542438 |
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Target ID: 151531.0 Gene Symbol: UPP2 |
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Target ID: CHEMBL2311222 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Curative | VISTOGARD Approved UseVISTOGARD® is a pyrimidine analog indicated for the emergency treatment of adult and pediatric patients:
• following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or
• who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system, and/or earlyonset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration Launch Date2015 |
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| Curative | VISTOGARD Approved UseVISTOGARD® is a pyrimidine analog indicated for the emergency treatment of adult and pediatric patients:
• following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or
• who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system, and/or earlyonset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration Launch Date2015 |
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| Primary | XURIDEN Approved UseXURIDEN is a pyrimidine analog for uridine replacement indicated for the treatment of hereditary orotic aciduria. Launch Date2015 |
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| Primary | XURIDEN Approved UseXURIDEN™ is indicated for the treatment of hereditary orotic aciduria. XURIDEN is a pyrimidine analog for uridine replacement indicated for the treatment of hereditary orotic aciduria. (1) Launch Date2015 |
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| Secondary | VISTOGARD Approved UseVISTOGARD® is indicated for the emergency treatment of adult and pediatric patients:
following a fluorouracil or capecitabine overdose regardless of the presence of symptoms, or
who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system, and/or early-onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration. Launch Date2015 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
36.1 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21379380 |
4.15 g single, oral dose: 4.15 g route of administration: Oral experiment type: SINGLE co-administered: |
URIDINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
25.8 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24009876 |
450 mg/kg single, oral dose: 450 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
URIDINE plasma | Oryctolagus cuniculus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
164.1 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21379380 |
4.15 g single, oral dose: 4.15 g route of administration: Oral experiment type: SINGLE co-administered: |
URIDINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
79 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24009876 |
450 mg/kg single, oral dose: 450 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
URIDINE plasma | Oryctolagus cuniculus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
4.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21379380 |
4.15 g single, oral dose: 4.15 g route of administration: Oral experiment type: SINGLE co-administered: |
URIDINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1.38 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24009876 |
450 mg/kg single, oral dose: 450 mg/kg route of administration: Oral experiment type: SINGLE co-administered: |
URIDINE plasma | Oryctolagus cuniculus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Bone morphogenetic protein-2, but not bone morphogenetic protein-7, promotes dendritic growth and calbindin phenotype in cultured rat striatal neurons. | 2001 |
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| [Oogenesis of Mozambique tilapia. II. Synthesis of RNA and development of the nucleoli]. | 2001 |
|
| Effects of ATP on intracellular calcium dynamics of neurons and satellite cells in rat superior cervical ganglia. | 2001 Apr |
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| Biphasic cytotoxic mechanism of extracellular ATP on U-937 human histiocytic leukemia cells: involvement of adenosine generation. | 2001 Apr 23 |
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| Thiosugars. Part 9: synthesis and biological evaluation of some 4'-thio-L-arabino nucleoside analogues. | 2001 Apr 23 |
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| High-performance liquid chromatographic assay for acetaminophen glucuronide in human liver microsomes. | 2001 Apr 5 |
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| Methyl orange antagonizes uridine 5' triphosphate and not alpha,beta-methylene-adenosine 5' triphosphate-evoked depolarization of rat superior cervical ganglia. | 2001 Feb |
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| UTP as an extracellular signaling molecule. | 2001 Feb |
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| Gap-junctional communication between feeder cells and recipient normal epithelial cells correlates with growth stimulation. | 2001 Feb |
|
| Natural and synthetic inhibitors of UDP-glucuronosyltransferase. | 2001 Feb |
|
| Importance of specific nucleotides in the folding of the natural form of the hairpin ribozyme. | 2001 Feb 20 |
|
| The eosinophil peroxidase-hydrogen peroxide-bromide system of human eosinophils generates 5-bromouracil, a mutagenic thymine analogue. | 2001 Feb 20 |
|
| A base change in the catalytic core of the hairpin ribozyme perturbs function but not domain docking. | 2001 Feb 27 |
|
| Synthesis of 2'-modified oligodeoxynucleotides via on-column conjugation. | 2001 Jan 26 |
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| Functional production of mammalian concentrative nucleoside transporters in Saccharomyces cerevisiae. | 2001 Jan-Mar |
|
| 5-(Trifluoromethyl)-beta-l-2'-deoxyuridine, the L-enantiomer of trifluorothymidine: stereospecific synthesis and antiherpetic evaluations. | 2001 Jul |
|
| Role of the hepatic function in the development of the pyrogenic tolerance to muramyl dipeptide. | 2001 Jul |
|
| Apical P2Y4 purinergic receptor controls K+ secretion by vestibular dark cell epithelium. | 2001 Jul |
|
| Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidine-mediated cell death and cell cycle responses. | 2001 Jul 1 |
|
| Equilibrative nucleoside transporters: mapping regions of interaction for the substrate analogue nitrobenzylthioinosine (NBMPR) using rat chimeric proteins. | 2001 Jul 10 |
|
| Structure of an RNA hairpin from HRV-14. | 2001 Jul 10 |
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| Intracellular trafficking determinants in APOBEC-1, the catalytic subunit for cytidine to uridine editing of apolipoprotein B mRNA. | 2001 Jul 15 |
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| Activation pathways of 5-fluorouracil in rat organs and in PC12 cells. | 2001 Jul 15 |
|
| Subcellular distribution and membrane topology of the mammalian concentrative Na+-nucleoside cotransporter rCNT1. | 2001 Jul 27 |
|
| Effect of 17-beta estradiol and epidermal growth factor on DNA and RNA labeling in astroglial cells during development, maturation and differentiation in culture. | 2001 Jul 31 |
|
| Nucleoside analogues as highly potent and selective inhibitors of herpes simplex virus thymidine kinase. | 2001 Jul 9 |
|
| Sarpogrelate inhibits serotonin-induced proliferation of porcine coronary artery smooth muscle cells: implications for long-term graft patency. | 2001 Jun |
|
| Possible existence of a novel receptor for uridine analogues in the central nervous system using two isomers, N3-(S)-(+)- and N3-(R)-(-)-alpha-hydroxy-beta-phenethyluridines. | 2001 Jun |
|
| Poly(A) polymerase activity and RNA polyadenylation in Streptomyces coelicolor A3(2). | 2001 Jun |
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| Elucidation of the initial step of oligonucleotide fragmentation in matrix-assisted laser desorption/ionization using modified nucleic acids. | 2001 Jun |
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| Differential effects of apical and basolateral uridine triphosphate on intestinal epithelial chloride secretion. | 2001 Jun |
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| Delayed re-endothelialization and T-cell infiltration following intracoronary radiation therapy in the porcine model. | 2001 Jun 1 |
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| Structure of a C-rich strand fragment of the human centromeric satellite III: a pH-dependent intercalation topology. | 2001 Jun 1 |
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| Fluoropyrimidine sensitivity of human MCF-7 breast cancer cells stably transfected with human uridine phosphorylase. | 2001 Jun 15 |
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| The effect of cytidine on the structure and function of an RNA ligase ribozyme. | 2001 Mar |
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| An extended structural signature for the tRNA anticodon loop. | 2001 Mar |
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| The UDPase activity of the Kluyveromyces lactis Golgi GDPase has a role in uridine nucleotide sugar transport into Golgi vesicles. | 2001 May |
|
| Detection of genome impairment in bovine early embryos by autoradiography: a methodological note. | 2001 May |
|
| Effects of purine and pyrimidine nucleotides on intracellular Ca2+ in human eosinophils: activation of purinergic P2Y receptors. | 2001 May |
|
| Lethality of glnD null mutations in Azotobacter vinelandii is suppressible by prevention of glutamine synthetase adenylylation. | 2001 May |
|
| Phosphorylation of uridine and cytidine nucleoside analogs by two human uridine-cytidine kinases. | 2001 May |
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| Uridine receptor: discovery and its involvement in sleep mechanism. | 2001 May 1 |
|
| Bacteriophage T7 RNA polymerase transcription elongation is inhibited by site-specific, stereospecific benzo[c]phenanthrene diol epoxide DNA lesions. | 2001 May 1 |
|
| Herpes simplex virus 1 ICP27 is required for transcription of two viral late (gamma 2) genes in infected cells. | 2001 May 10 |
|
| High-performance liquid chromatographic method combining radiochemical and ultraviolet detection for determination of low activities of uridine 5'-diphosphate-glucuronosyltransferase. | 2001 May 15 |
|
| Liquid-core waveguide technology for coupling column liquid chromatography and Raman spectroscopy. | 2001 May 18 |
|
| Probing Tat peptide-TAR RNA interactions by psoralen photo-cross-linking. | 2001 May 29 |
|
| Uridine Triacetate. | 2016 Jun |
|
| Emergency use of uridine triacetate for the prevention and treatment of life-threatening 5-fluorouracil and capecitabine toxicity. | 2017 Jan 1 |
|
| Successful use of uridine triacetate (Vistogard) three weeks after capecitabine in a patient with homozygous dihydropyrimidine dehydrogenase mutation: A case report and review of the literature. | 2019 Jan |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208169Orig1s000Lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf
Curator's Comment: 10 grams orally every 6 hours for 20 doses, without regard to meals.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208159s000lbl.pdf
The recommended starting dosage of oral XURIDEN for the treatment of hereditary orotic aciduria is 60 mg/kg once daily. Increase the dosage of
XURIDEN to 120 mg/kg (not to exceed 8 grams) once daily for insufficient efficacy.
The recommended dosage of VISTOGARD for the emergency treatment of fluorouracil or capecitabine overdose.
Adults: 10 grams (1 packet) orally every 6 hours for 20 doses, without regard to meals.
Pediatric: 6.2 grams/m2 of body surface area (not to exceed 10 grams per dose) orally every 6 hours
for 20 doses, without regard to meals.
Route of Administration:
Oral
Uridine dose-dependently protected cells from chemical hypoxia and ceramide, and decreased formation of reactive oxygen species and mitochondrial DNA damage due to hydrogen peroxide. These protective effects were achieved by raising uridine levels to at least 25-50 μM and serum uridine levels in this range in humans were obtained with oral uridine prodrug PN401 (Uridine triacetate).
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| Classification Tree | Code System | Code | ||
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LOINC |
59216-2
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NCI_THESAURUS |
C2080
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NDF-RT |
N0000191809
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DSLD |
3300 (Number of products:5)
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LOINC |
75159-4
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75130-5
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1707114
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N0000175452
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PRIMARY | Analogs/Derivatives [Chemical/Ingredient] | ||
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WHI7HQ7H85
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DB02745
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11017
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16704
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D014529
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20256
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SUB05047MIG
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58-96-8
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DTXSID40891555
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m11332
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WHI7HQ7H85
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200-407-5
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URIDINE
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N0000007587
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PRIMARY | Pyrimidines [Chemical/Ingredient] | ||
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6029
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C922
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ACTIVE MOIETY
PARENT (METABOLITE)
PRODRUG (METABOLITE ACTIVE)
