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| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682006 |
| Routes of administration | Intra-arterial |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.000.066 |
| Chemical and physical data | |
| Formula | C9H11FN2O5 |
| Molar mass | 246.194 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 150.5 °C (302.9 °F) |
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Floxuridine (also5-fluorodeoxyuridine) is anoncology drug that belongs to the class known asantimetabolites. Specifically, floxuridine is apyrimidine analog, classified as adeoxyuridine.[1] The drug is usually administered via an artery, and most often used in the treatment ofcolorectal cancer. The quality of life and survival rates of individuals that receive continuoushepatic arteryinfusion of floxuridine forcolorectal cancermetastases is significantly higher than control groups.[2] Floxuridine can also be prescribed for the treatment of kidney and stomachcancers.[3]In vitro uses of floxuridine include 5-minute treatments offluorouracil, floxuridine, andmitomycin to increase cell proliferation inTenon's capsulefibroblasts.[4]
ImmobilizedAeromonas salmonicida ATCC 27013, when exposed tothymidine and 5-fluorouracil in phosphate buffer at room temperature for one hour, can synthesize floxuridine andthymine.[5]
Floxuridine primarily works by stopping the growth of newly born cells.[6] The drug essentially stopsDNA 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 andhepatic metastases, an average adult should be given an intra-arterial dosage of 0.1–0.6 mg/kg/day as a continuousinfusion, continued until intolerable toxicity is reached (white blood cell count < 3,500/mm3 or platelet count < 100,000/mm3).[7]Lethal dosages for other species are below.[8]LD50 is the lethal dose at which half oforganisms exposed to the drug die.
| Species | LD50 (mg/kg +/- SE) |
|---|---|
| Mouse | 880 +/- 51 |
| Rat | 670 +/- 73 |
| Rabbit | 94 +/- 19.6 |
| Dog | 157 +/- 46 |
Floxuridine is apyrimidine analog that acts as an inhibitor of theS-phase of cell division. This selectively kills rapidly dividing cells.Antimetabolites masquerade aspyrimidine-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 anenzyme which convertscytosine nucleosides into the deoxyderivative. In addition, DNA synthesis is further inhibited because fluorouracil blocks the incorporation of thethymidinenucleotide into the DNA strand.
Floxuridine is rapidly catabolized to5-fluorouracil, which is the active form of the drug. The primary effect is interference with DNA synthesis and to a lesser extent, inhibition ofRNA formation through the drug's incorporation intoRNA, thus leading to the production of fraudulent RNA. Fluorouracil also inhibitsuracil riboside phosphorylase, which prevents the utilization of preformeduracil in RNA synthesis. As well, themonophosphate of floxuridine,5-fluoro-2'-deoxyuridine-5'-phosphate (FUDR-MP) inhibits the enzymethymidylate synthetase. This leads to the inhibition ofmethylation ofdeoxyuridylic acid tothymidylic acid, thus interfering withDNA synthesis.
The drug is excreted intact and asurea,fluorouracil, α-fluoro-β-ureidopropionic acid, dihydrofluorouracil, α-fluoro-β-guanidopropionic acid, and α-fluoro-β-alanine in theurine; it is also expired as respiratorycarbon dioxide.
Side effects include:[9]
Apart from its use in chemotherapy, floxuridine is also used inaging research employing aC. elegans model, namely to stop growth and to prevent reproduction. The latter is brought about by treatment of larvae close to maturity with low doses of floxuridine that, even though allowing normal maturation, causes reproducing individuals to lay eggs that are unable to hatch.[10] This limits the population to a single generation allowing quantification of aging processes and measurement oflongevity.[11] It has, however, been indicated that floxuridin exposure by itself increases life expectancy potentially leading to flawed data in respective studies.[12]
Floxuridine first gainedFDA approval in December 1970 under the brand name FUDR. The drug was initially marketed byRoche, which also did a lot of the initial work on5-fluorouracil. TheNational Cancer Institute was an early developer of the drug. Roche sold its FUDR product line in 2001 toF H Faulding, which becameMayne Pharma.
Synonyms for floxuridine include:[13]
