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<!--Chemical data-->
<!--Chemical data-->
| C=9 | H=11 | F=1 | N=2 | O=5
| C=9 | H=11 | F=1 | N=2 | O=5
| molecular_weight = 246.192 g/mol
| Molecular_weight = 246.192 g/mol
| MeltingPt = 150.5 (Celsius)
| pKa = 7.44
| smiles = FC=1C(=O)NC(=O)N(C=1)[C@@H]2O[C@@H]([C@@H](O)C2)CO
| smiles = FC=1C(=O)NC(=O)N(C=1)[C@@H]2O[C@@H]([C@@H](O)C2)CO
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
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}}
}}


'''Floxuridine''' (also ''5-fluorodeoxyuridine'') is an [[oncology]] drug that belongs to the class known as [[antimetabolite]]s. Specifically, floxuridine is a [[pyrimidine]] analog, classified as a [[deoxyuridine]]<ref>{{cite web|title=Floxuridine|url=https://pubchem.ncbi.nlm.nih.gov/compound/floxuridine#section=Top|website=PubChem|accessdate=18 April 2017}}</ref>. The drug is usually administered via an artery, and most often used in the treatment of [[colorectal cancer]]. The quality of life and survival rates of individuals that receive continuous [[hepatic artery]] [[infusion]] of floxuridine for [[colorectal cancer]] [[metastases]] is significantly higher than control groups.<ref>{{cite journal|last1=Allen-Mersh|first1=TG|last2=Earlam|first2=S|last3=Fordy|first3=C|last4=Abrams|first4=K|last5=Houghton|first5=J|title=Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases|journal=The Lancet|date=November 1994|volume=344|issue=8932|pages=1255-1260|doi=10.1016/S0140-6736(94)90750-1|url=http://www.sciencedirect.com/science/article/pii/S0140673694907501}}</ref> Fluxuridine can also be prescribed for the treatment of kidney and stomach [[cancers]].<ref>{{cite web|title=Floxuridine|url=http://chemocare.com/chemotherapy/drug-info/floxuridine.aspx|website=Chemocare|publisher=Chemocare.com|accessdate=17 April 2017}}</ref> [[In vitro]] uses of floxuridine include 5-minute treatments of [[fluorouracil]], floxuridine, and [[mitomycin]] to increase cell proliferation in [[Tenon's capsule]] [[fibroblasts]]. <ref>{{cite journal|last1=Khaw|first1=Peng T.|last2=Sherwood|first2=Mark B.|last3=Mackay|first3=Sally L. D.|title=Five-Minute Treatments With Fluorouracil, Floxuridine, and Mitomycin Have Long-term Effects on Human Tenon's Capsule Fibroblasts|journal=JAMA Opthamalogy|date=August 1992|doi=10.1001/archopht.1992.01080200130040|url=http://jamanetwork.com/journals/jamaophthalmology/article-abstract/639809|accessdate=7 May 2017}}</ref>
'''Floxuridine''' (also ''5-fluorodeoxyuridine'') is an [[oncology]] drug that belongs to the class known as [[antimetabolite]]s. The drug is most often used in the treatment of colorectal cancer.


==Biosynthesis<ref>{{cite journal|last1=Rivero|first1=Cintia|last2=Britos|first2=Claudia|last3=Mario|first3=Lozano|last4=Sinisterra|first4=Jose|last5=Trelles|first5=Jorge|title=Green biosynthesis of floxuridine by immobilized microorganisms|journal=Microbiology Letters|date=March 12, 2012|issue=331|pages=31-36|doi=10.1111/j.1574-6968.2012.02547.x|accessdate=17 April 2017}}</ref> ==
==Pharmacology==
Immobilized [[Aeromonas salmonicida]] ATCC 27013, when exposed to [[thymidine]] and 5-fluorouracil in phosphate buffer at room temperature for one hour, can synthesize floxuridine and [[thymine]]. [[File:Floxuridine Biosynthesis.png|thumb|Biosynthesis of Floxuridine]]
Floxuridine, an analog of 5-[[fluorouracil]], is a fluorinated [[pyrimidine]].


==Pharmacology<ref>{{cite web|last1=Canadian Institutes of Health Research|title=Floxuridine|url=https://www.drugbank.ca/drugs/DB00322|website=DrugBank|accessdate=18 April 2017}}</ref>==
==Mechanism of action==
Floxuridine primarily works by stopping the growth of newly born cells. The drug essentially stops [[DNA]] from forming in new and rapidly developing cells, which is a sign of a cancerous cell. Therefore, the floxuridine kills the cancerous cells. For colorectal cancer and [[hepatic metastases]], an average adult should be given an Intra-arterial dosage of 0.1-0.6 mg/kg/day as a continuous [[infusion]], continued until intolerable toxicity is reached ([[white blood cell]] count <3,500/mm^3 or platelet count <100,000/mm^3)<ref>{{cite web|title=Floxuridine|url=https://www.drugs.com/ppa/floxuridine.html|website=Drugs.com}}</ref>.
Floxuridine works because it is broken down by the body into its active form, which is the same as a metabolite of 5-Fluorouracil.
Lethal dosages for other species are below<ref>{{cite web|title=Floxuridine|url=https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=134053|publisher=Bedford Laboratories}}</ref>. [[LD50]] is the lethal dose at which half of [[organisms]] exposed to the drug die.
{| class="wikitable"
|-
! [[Species]] !! [[LD50]] (mg/kg +/- SE)
|-
| [[Mouse]] || 880 +/- 51
|-
| [[Rat]] || 670 +/- 73
|-
| [[Rabbit]] || 94 +/- 19.6
|-
| [[Dog]] || 157 +/- 46
|}

===Pharmacodynamics===
Floxuridine is a [[pyrimidine]] analog that acts as an inhibitor of the [[S-phase]] of cell division. This selectively kills rapidly dividing cells. [[Antimetabolites]] masquerade as [[pyrimidine]]-like molecules which prevents normal pyrimidines from being incorporated into DNA during the S phase of the cell cycle. [[Fluorouracil]] (the end-product of catabolism of floxuridine) blocks an [[enzyme]] which converts [[cytosine]] nucleosides into the deoxy [[derivative]]. In addition, DNA synthesis is further inhibited because fluoruracil blocks the incorporation of the [[thymidine]] [[nucleotide]] into the DNA strand.

===Mechanism of Action ===
Floxuridine is rapidly catabolized to [[5-fluorouracil]], which is the active form of the drug. The primary effect is interference with DNA synthesis and to a lesser extent, inhibition of [[RNA]] formation through the drug's incorporation into [[RNA]], thus leading to the production of fraudulent RNA. Fluorouracil also inhibits [[uracil riboside phosphorylase]], which prevents the utilization of preformed [[uracil]] in RNA synthesis. As well, the [[monophosphate]] of floxuridine, [[5-fluoro-2'-deoxyuridine-5'-phosphate (FUDR-MP)]] inhibits the enzyme [[thymidylate synthetase]]. This leads to the inhibition of [[methylation]] of [[deoxyuridylic acid]] to [[thymidylic acid]], thus interfering with [[DNA synthesis]].

===Route of Elimination===
The drug is excreted intact and as [[urea]], [[fluorouracil]], [[a-fluoro-bureidopropionic acid]], [[dihydrofluorouracil]], [[a-fluoro-b-guanidopropionic acid]] and [[a-fluoro-b-alanine]] in the [[urine]]; it is also expired as respiratory [[carbon dioxide]].

==Side Effects<ref>{{cite web|title=Floxuridine|url=http://chemocare.com/chemotherapy/drug-info/floxuridine.aspx|website=Chemocare|publisher=Chemocare.com|accessdate=17 April 2017}}</ref>==
===Common (30% of patients)===
* Low blood counts. Your white and [[red blood cells]] and [[platelets]] may temporarily decrease. This can put you at increased risk for infection, [[anemia]] and/or bleeding.
* Mouth sores
* Diarrhea (may be severe)
===Less common (10-29% of patients)===
* Poor [[appetite]]
* [[Nausea]] and [[vomiting]]
* [[Hair loss]]
* Elevated liver enzymes (temporary increase in [[alkaline phosphatase]], [[lactate dehydrogenase]], [[transaminase]], and [[bilirubin]]). This is seen more with the intra-arterial infusion directly into the liver.
* [[Hand-foot syndrome]] (Palmar-plantar erythrodysesthesia or PPE) -skin rash, [[swelling]], redness, pain and/or peeling of the skin on the palms of hands and soles of feet
* [[Stomach ulcers]] (This is seen more with the intra-arterial infusion).
===Contact your health provider immediately===
* [[Fever]] of 100.4° F (38° C) or higher, chills (possible signs of infection).
===Contact your health provider===
* [[Diarrhea]] (2 episodes in a 24-hour period)
* [[Nausea]] (interferes with ability to eat and unrelieved with prescribed medication)
* [[Vomiting]] (vomiting more than 4-5 times in a 24 hour period)
* [[Mouth sores]] (painful redness, swelling or ulcers)
* Unusual bleeding or bruising
* Black or tarry stools, or blood in your stools
* Blood in the [[urine]]
* Yellowing of the skin or eyes
* Tingling or burning, redness, swelling of the palms of the hands or soles of feet
===Other===
* Fertility for both men and women may be affected by floxuridine.

==If Poisoned==
Seek medical attention and stop intra-arterial infusions of floxuridine at the first signs of [[overdose]].


==History==
==History==
Floxuridine first gained FDA approval in December 1970 under the brand name FUDR. The drug was initially marketed by Roche, which also did a lot of the initial work on 5-fluorouracil. The [[National Cancer Institute]] was an early developer of the drug. Roche sold its FUDR product line in 2001 to [[F H Faulding]], which became [[Mayne Pharma]].
Floxuridine first gained [[FDA]] approval in December 1970 under the brand name FUDR. The drug was initially marketed by [[Roche]], which also did a lot of the initial work on [[5-fluorouracil]]. The [[National Cancer Institute]] was an early developer of the drug. [[Roche]] sold its FUDR product line in 2001 to [[F H Faulding]], which became [[Mayne Pharma]].

==Suppliers<ref>{{cite web|title=Floxuridine|url=https://pubchem.ncbi.nlm.nih.gov/compound/floxuridine#section=Top|website=PubChem|accessdate=18 April 2017}}</ref>==
[[File:Floxuridine Label.jpg|thumb|Label of Floxuridine]]
{{col-begin|width=auto}}
{{col-break}}
* [[APP Pharmaceuticals]]
* [[LLC; Hospira, Inc.]]
* [[Bedford Laboratories]]
* [[Wilshire Technologies]]
* [[ChangChem]]
* [[CAPOT]]
* [[PubChem]]
* [[King Scientific]]
* [[Assembly Blocks Pvt. Ltd.]]
* [[OXCHEM CORPORATION]]
* [[Glentham Life Sciences Ltd.]]
* [[Achemo Scientific Limited]]
* [[TargetMol]]
* [[BerrChem]]
* [[Chembase.cn]]
* [[A&J Pharmtech CO., LTD.]]
* [[Sigma-Aldrich]]
{{col-break}}
* [[BioChemPartner]]
* [[Biosynth]]
* [[Parchem]]
* [[Ambinter]]
* [[Vitas-M Laboratory]]
* [[Hangzhou Trylead Chemical Technology]]
* [[Wutech]]
* [[Angene Chemical]]
* [[Key Organics/BIONET]]
* [[ChemScene]]
* [[Aurum Pharmatech LLC]]
* [[Debye Scientific Co., Ltd]]
* [[Green Chempharm Inc]]
* [[1717 CheMall Corporation]]
* [[ChemShuttle]]
{{col-break}}
* [[NORRIS PHARM]]
* [[labseeker]]
* [[Pure chemistry]]
* [[Bide Pharmatech Ltd.]]
* [[AX Molecules Inc]]
* [[Anward]]
* [[Mcule]]
* [[Ark Pharm, Inc.]]
* [[Boc Sciences]]
* [[ChemTik]]
* [[AKos Consulting & Solutions]]
* [[Tocris Bioscience]]
* [[BePharm Ltd.]]
* [[ZINC]]
* [[CambridgeChem]]
* [[Chem-Space.com Database]]
* [[TimTec]]
* [[Founder Pharma]]
{{col-break}}
* [[Phion Ltd]]
* [[Alsachim]]
* [[NIH Clinical Collection]]
* [[Hangzhou APIChem Technology]]
* [[AK Scientific, Inc. (AKSCI)]]
* [[Acadechem]]
* [[AbovChem LLC]]
* [[AstaTech, Inc.]]
* [[TCI (Tokyo Chemical Industry)]]
* [[MedChemexpress MCE]]
* [[AEchem Scientific Corporation, USA]]
* [[Oakwood Products]]
* [[Molepedia]]
* [[Race Chemical]]
* [[Enamine]]
* [[AHH Chemical co.,ltd]]
{{col-end}}


==Alternative Names<ref>{{cite web|last1=Canadian Institutes of Health Research|title=Floxuridine|url=https://www.drugbank.ca/drugs/DB00322|website=DrugBank|accessdate=18 April 2017}}</ref>==
==Suppliers==
{{col-begin|width=auto}}
In the US the drug is supplied by APP Pharmaceuticals, LLC; Hospira, Inc.; and Bedford Laboratories.
{{col-break}}
* 5 Fluorodeoxyuridine
* 5-Fluorodeoxyuridine
* 5-FUdR
* Floxuridine
* Fluorodeoxyuridine
* FUdR
* 50-91-9
* 2'-Deoxy-5-fluorouridine
* 5-Fluoro-2'-deoxyuridine
* 5-Fluorodeoxyuridine
* FUDR
* 5 Fluorodeoxyuridine
{{col-break}}
* Fluorodeoxyuridine
* Floxuridin
* Fluoruridine deoxyribose
* Deoxyfluorouridine
* Floxiridina
* Floxuridinum
* 5-Fluorouracil deoxyriboside
* 5-Fluoro-2-desoxyuridine
* 5FdU
* 5-Fluoro-2-deoxyuridine
* beta-5-Fluoro-2'-deoxyuridine
* FDUR
{{col-break}}
* 5-fluoro-1-((2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidine-2,4(1h,3h)-dione
* FdUrd
* 1-(2-Deoxy-beta-D-ribofuranosyl)-5-fluorouracil
* Uridine, 2'-deoxy-5-fluoro-
* 1beta-D-2'-Deoxyribofuranosyl-5-flurouracil
* 1-beta-D-2'-Deoxyribofuranosyl-5-flurouracil
* UNII-039LU44I5M
* 5-Fluorouracil 2'-deoxyriboside
* Floxuridinum [INN-Latin]
* Floxiridina [INN-Spanish]
* 5-FdUrd
{{col-end}}


{{Chemotherapeutic agents}}
{{Chemotherapeutic agents}}

Revision as of 17:48, 7 May 2017

Floxuridine
Clinical data
AHFS/Drugs.comMonograph
MedlinePlusa682006
Pregnancy
category
  • (US): D
Routes of
administration		Intra-arterial
ATC code
  • none
Legal status
Legal status
Identifiers
  • 5-Fluoro-1-[4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-pyrimidine-2,4-dione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.066 Edit this at Wikidata
Chemical and physical data
FormulaC9H11FN2O5
Molar mass246.194 g·mol−1
3D model (JSmol)
  • FC=1C(=O)NC(=O)N(C=1)[C@@H]2O[C@@H]([C@@H](O)C2)CO
  • InChI=1S/C9H11FN2O5/c10-4-2-12(9(16)11-8(4)15)7-1-5(14)6(3-13)17-7/h2,5-7,13-14H,1,3H2,(H,11,15,16)/t5-,6+,7+/m0/s1 checkY
  • Key:ODKNJVUHOIMIIZ-RRKCRQDMSA-N checkY
  (verify)

Floxuridine (also 5-fluorodeoxyuridine) is an oncology drug that belongs to the class known as antimetabolites. Specifically, floxuridine is a pyrimidine analog, classified as a deoxyuridine[2]. The drug is usually administered via an artery, and most often used in the treatment of colorectal cancer. The quality of life and survival rates of individuals that receive continuous hepatic artery infusion of floxuridine for colorectal cancer metastases is significantly higher than control groups.[3] Fluxuridine can also be prescribed for the treatment of kidney and stomach cancers.[4] In vitro uses of floxuridine include 5-minute treatments of fluorouracil, floxuridine, and mitomycin to increase cell proliferation in Tenon's capsule fibroblasts. [5]

Biosynthesis[6]

Immobilized Aeromonas salmonicida ATCC 27013, when exposed to thymidine and 5-fluorouracil in phosphate buffer at room temperature for one hour, can synthesize floxuridine and thymine.

Biosynthesis of Floxuridine

Pharmacology[7]

Floxuridine primarily works by stopping the growth of newly born cells. The drug essentially stops DNA from forming in new and rapidly developing cells, which is a sign of a cancerous cell. Therefore, the floxuridine kills the cancerous cells. For colorectal cancer and hepatic metastases, an average adult should be given an Intra-arterial dosage of 0.1-0.6 mg/kg/day as a continuous infusion, continued until intolerable toxicity is reached (white blood cell count <3,500/mm^3 or platelet count <100,000/mm^3)[8]. Lethal dosages for other species are below[9]. LD50 is the lethal dose at which half of organisms exposed to the drug die.

Species LD50 (mg/kg +/- SE)
Mouse 880 +/- 51
Rat 670 +/- 73
Rabbit 94 +/- 19.6
Dog 157 +/- 46

Pharmacodynamics

Floxuridine is a pyrimidine analog that acts as an inhibitor of the S-phase of cell division. This selectively kills rapidly dividing cells. Antimetabolites masquerade as pyrimidine-like molecules which prevents normal pyrimidines from being incorporated into DNA during the S phase of the cell cycle. Fluorouracil (the end-product of catabolism of floxuridine) blocks an enzyme which converts cytosine nucleosides into the deoxy derivative. In addition, DNA synthesis is further inhibited because fluoruracil blocks the incorporation of the thymidine nucleotide into the DNA strand.

Mechanism of Action

Floxuridine is rapidly catabolized to 5-fluorouracil, which is the active form of the drug. The primary effect is interference with DNA synthesis and to a lesser extent, inhibition of RNA formation through the drug's incorporation into RNA, thus leading to the production of fraudulent RNA. Fluorouracil also inhibits uracil riboside phosphorylase, which prevents the utilization of preformed uracil in RNA synthesis. As well, the monophosphate of floxuridine, 5-fluoro-2'-deoxyuridine-5'-phosphate (FUDR-MP) inhibits the enzyme thymidylate synthetase. This leads to the inhibition of methylation of deoxyuridylic acid to thymidylic acid, thus interfering with DNA synthesis.

Route of Elimination

The drug is excreted intact and as urea, fluorouracil, a-fluoro-bureidopropionic acid, dihydrofluorouracil, a-fluoro-b-guanidopropionic acid and a-fluoro-b-alanine in the urine; it is also expired as respiratory carbon dioxide.

Side Effects[10]

Common (30% of patients)

  • Low blood counts. Your white and red blood cells and platelets may temporarily decrease. This can put you at increased risk for infection, anemia and/or bleeding.
  • Mouth sores
  • Diarrhea (may be severe)

Less common (10-29% of patients)

Contact your health provider immediately

  • Fever of 100.4° F (38° C) or higher, chills (possible signs of infection).

Contact your health provider

  • Diarrhea (2 episodes in a 24-hour period)
  • Nausea (interferes with ability to eat and unrelieved with prescribed medication)
  • Vomiting (vomiting more than 4-5 times in a 24 hour period)
  • Mouth sores (painful redness, swelling or ulcers)
  • Unusual bleeding or bruising
  • Black or tarry stools, or blood in your stools
  • Blood in the urine
  • Yellowing of the skin or eyes
  • Tingling or burning, redness, swelling of the palms of the hands or soles of feet

Other

  • Fertility for both men and women may be affected by floxuridine.

If Poisoned

Seek medical attention and stop intra-arterial infusions of floxuridine at the first signs of overdose.

History

Floxuridine first gained FDA approval in December 1970 under the brand name FUDR. The drug was initially marketed by Roche, which also did a lot of the initial work on 5-fluorouracil. The National Cancer Institute was an early developer of the drug. Roche sold its FUDR product line in 2001 to F H Faulding, which became Mayne Pharma.

Suppliers[11]

Label of Floxuridine

Alternative Names[12]

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ "Floxuridine". PubChem. Retrieved 18 April 2017.
  3. ^ Allen-Mersh, TG; Earlam, S; Fordy, C; Abrams, K; Houghton, J (November 1994). "Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases". The Lancet. 344 (8932): 1255–1260. doi:10.1016/S0140-6736(94)90750-1.
  4. ^ "Floxuridine". Chemocare. Chemocare.com. Retrieved 17 April 2017.
  5. ^ Khaw, Peng T.; Sherwood, Mark B.; Mackay, Sally L. D. (August 1992). "Five-Minute Treatments With Fluorouracil, Floxuridine, and Mitomycin Have Long-term Effects on Human Tenon's Capsule Fibroblasts". JAMA Opthamalogy. doi:10.1001/archopht.1992.01080200130040. Retrieved 7 May 2017.
  6. ^ Rivero, Cintia; Britos, Claudia; Mario, Lozano; Sinisterra, Jose; Trelles, Jorge (March 12, 2012). "Green biosynthesis of floxuridine by immobilized microorganisms". Microbiology Letters (331): 31–36. doi:10.1111/j.1574-6968.2012.02547.x. {{cite journal}}: |access-date= requires |url= (help)
  7. ^ Canadian Institutes of Health Research. "Floxuridine". DrugBank. Retrieved 18 April 2017.
  8. ^ "Floxuridine". Drugs.com.
  9. ^ "Floxuridine". Bedford Laboratories.
  10. ^ "Floxuridine". Chemocare. Chemocare.com. Retrieved 17 April 2017.
  11. ^ "Floxuridine". PubChem. Retrieved 18 April 2017.
  12. ^ Canadian Institutes of Health Research. "Floxuridine". DrugBank. Retrieved 18 April 2017.
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