Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C9H11FN2O5 |
Molecular Weight | 246.1924 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC[C@H]1O[C@H](C[C@@H]1O)N2C=C(F)C(=O)NC2=O
InChI
InChIKey=ODKNJVUHOIMIIZ-RRKCRQDMSA-N
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
DescriptionSources: http://www.drugbank.ca/drugs/DB00322Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/pro/floxuridine.html
Sources: http://www.drugbank.ca/drugs/DB00322
Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/pro/floxuridine.html
Floxuridine is a pyrimidine analog that acts as an inhibitor of the S-phase of cell division. This selectively kills rapidly dividing cells. Floxuridine is an anti-metabolite. Anti-metabolites masquerade as pyramidine-like molecules which prevents normal pyrimidines from being incorporated into DNA during the S phase of the cell cycle. Flurouracil (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 thymdine nucleotide into the DNA strand. Floxuridine is used for palliative management of gastrointestinal adenocarcinoma metastatic to the liver, when given by continuous regional intra-arterial infusion in carefully selected patients who are considered incurable by surgery or other means. Also for the palliative management of liver cancer (usually administered by hepatic intra-arterial infusion).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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1952 Sources: http://www.drugbank.ca/drugs/DB00322 |
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Target ID: CHEMBL3160 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?21330014 |
0.4 nM [IC50] | ||
Target ID: CHEMBL614353 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14716816 |
5.02 µM [IC50] | ||
Target ID: CHEMBL614909 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14716816 |
12.45 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | FLOXURIDINE Approved UseFloxuridine for Injection, USP is effective in the palliative management of gastrointestinal adenocarcinoma metastatic to the liver, when given by continuous regional intra-arterial infusion in carefully selected patients who are considered incurable by surgery or other means. Launch Date9.5489281E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5547 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19147776 |
10.8 mg/m² 1 times / 2 weeks multiple, intravenous dose: 10.8 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: Irinotecan | 7-Ethyl-10-hydroxycamptothecin | 5-Fluorouracil |
FLOXURIDINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
79304 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19147776 |
10.8 mg/m² 1 times / 2 weeks multiple, intravenous dose: 10.8 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: Irinotecan | 7-Ethyl-10-hydroxycamptothecin | 5-Fluorouracil |
FLOXURIDINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19147776 |
10.8 mg/m² 1 times / 2 weeks multiple, intravenous dose: 10.8 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: Irinotecan | 7-Ethyl-10-hydroxycamptothecin | 5-Fluorouracil |
FLOXURIDINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
1750 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 1750 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 1750 mg/m2, 1 times / week Co-administed with:: leucovorin, i.v(500 mg/m2 by 2-h infusion; weekly x 6) Sources: Page: p.263 |
unhealthy, 30-79 n = 3 Health Status: unhealthy Condition: Carcinoma Age Group: 30-79 Sex: M+F Population Size: 3 Sources: Page: p.263 |
DLT: Diarrhea... Dose limiting toxicities: Diarrhea (grade 4, 50%) Sources: Page: p.263 |
1650 mg/m2 1 times / week multiple, intravenous MTD Dose: 1650 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 1650 mg/m2, 1 times / week Co-administed with:: leucovorin, i.v(500 mg/m2 by 2-h infusion; weekly x 6) Sources: Page: p.263 |
unhealthy, 30-79 n = 6 Health Status: unhealthy Condition: Carcinoma Age Group: 30-79 Sex: M+F Population Size: 6 Sources: Page: p.263 |
DLT: Diarrhea... Dose limiting toxicities: Diarrhea (grade 3, 33.3%) Sources: Page: p.263 |
544 mg/m2 5 times / day multiple, intraarterial (mean) MTD Dose: 544 mg/m2, 5 times / day Route: intraarterial Route: multiple Dose: 544 mg/m2, 5 times / day Co-administed with:: 5-FU, i.v(6025 mg/m2/cycle (5 days)) Sources: Page: p.390 |
unhealthy, 44-75 n = 29 Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Age Group: 44-75 Sex: M+F Population Size: 29 Sources: Page: p.390 |
DLT: Mucositis... Dose limiting toxicities: Mucositis (grade 3-4, 72%) Sources: Page: p.390 |
0.6 mg/kg 1 times / day multiple, intraarterial (max) Recommended Dose: 0.6 mg/kg, 1 times / day Route: intraarterial Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Sources: |
Disc. AE: Fetal damage, Myocardial ischemia... AEs leading to discontinuation/dose reduction: Fetal damage Sources: Myocardial ischemia Stomatitis Esophagitis Leukopenia Vomiting Diarrhea Gastrointestinal ulcer Gastrointestinal bleeding Thrombocytopenia Hemorrhage |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Diarrhea | grade 4, 50% DLT, Disc. AE |
1750 mg/m2 1 times / week multiple, intravenous Highest studied dose Dose: 1750 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 1750 mg/m2, 1 times / week Co-administed with:: leucovorin, i.v(500 mg/m2 by 2-h infusion; weekly x 6) Sources: Page: p.263 |
unhealthy, 30-79 n = 3 Health Status: unhealthy Condition: Carcinoma Age Group: 30-79 Sex: M+F Population Size: 3 Sources: Page: p.263 |
Diarrhea | grade 3, 33.3% DLT, Disc. AE |
1650 mg/m2 1 times / week multiple, intravenous MTD Dose: 1650 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 1650 mg/m2, 1 times / week Co-administed with:: leucovorin, i.v(500 mg/m2 by 2-h infusion; weekly x 6) Sources: Page: p.263 |
unhealthy, 30-79 n = 6 Health Status: unhealthy Condition: Carcinoma Age Group: 30-79 Sex: M+F Population Size: 6 Sources: Page: p.263 |
Mucositis | grade 3-4, 72% DLT |
544 mg/m2 5 times / day multiple, intraarterial (mean) MTD Dose: 544 mg/m2, 5 times / day Route: intraarterial Route: multiple Dose: 544 mg/m2, 5 times / day Co-administed with:: 5-FU, i.v(6025 mg/m2/cycle (5 days)) Sources: Page: p.390 |
unhealthy, 44-75 n = 29 Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Age Group: 44-75 Sex: M+F Population Size: 29 Sources: Page: p.390 |
Diarrhea | Disc. AE | 0.6 mg/kg 1 times / day multiple, intraarterial (max) Recommended Dose: 0.6 mg/kg, 1 times / day Route: intraarterial Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Sources: |
Esophagitis | Disc. AE | 0.6 mg/kg 1 times / day multiple, intraarterial (max) Recommended Dose: 0.6 mg/kg, 1 times / day Route: intraarterial Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Sources: |
Fetal damage | Disc. AE | 0.6 mg/kg 1 times / day multiple, intraarterial (max) Recommended Dose: 0.6 mg/kg, 1 times / day Route: intraarterial Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Sources: |
Gastrointestinal bleeding | Disc. AE | 0.6 mg/kg 1 times / day multiple, intraarterial (max) Recommended Dose: 0.6 mg/kg, 1 times / day Route: intraarterial Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Sources: |
Gastrointestinal ulcer | Disc. AE | 0.6 mg/kg 1 times / day multiple, intraarterial (max) Recommended Dose: 0.6 mg/kg, 1 times / day Route: intraarterial Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Sources: |
Hemorrhage | Disc. AE | 0.6 mg/kg 1 times / day multiple, intraarterial (max) Recommended Dose: 0.6 mg/kg, 1 times / day Route: intraarterial Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Sources: |
Leukopenia | Disc. AE | 0.6 mg/kg 1 times / day multiple, intraarterial (max) Recommended Dose: 0.6 mg/kg, 1 times / day Route: intraarterial Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Sources: |
Myocardial ischemia | Disc. AE | 0.6 mg/kg 1 times / day multiple, intraarterial (max) Recommended Dose: 0.6 mg/kg, 1 times / day Route: intraarterial Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Sources: |
Stomatitis | Disc. AE | 0.6 mg/kg 1 times / day multiple, intraarterial (max) Recommended Dose: 0.6 mg/kg, 1 times / day Route: intraarterial Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Sources: |
Thrombocytopenia | Disc. AE | 0.6 mg/kg 1 times / day multiple, intraarterial (max) Recommended Dose: 0.6 mg/kg, 1 times / day Route: intraarterial Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Sources: |
Vomiting | Disc. AE | 0.6 mg/kg 1 times / day multiple, intraarterial (max) Recommended Dose: 0.6 mg/kg, 1 times / day Route: intraarterial Route: multiple Dose: 0.6 mg/kg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Gastrointestinal adenocarcinoma metastatic to the liver Sources: |
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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Vaccinia virus inhibitors as a paradigm for the chemotherapy of poxvirus infections. | 2001 Apr |
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Impact of thymidine phosphorylase surexpression on fluoropyrimidine activity and on tumour angiogenesis. | 2001 Aug 3 |
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Surgical debulking and intraperitoneal chemotherapy for established peritoneal metastases from colon and appendix cancer. | 2001 Dec |
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Surgery as adjuvant therapy? The treatment of peritoneal metastases from gastrointestinal malignancy. | 2001 Dec |
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Antisense-induced down-regulation of thymidylate synthase and enhanced cytotoxicity of 5-FUdR in 5-FUdR-resistant HeLa cells. | 2001 Dec |
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Regional chemotherapy of nonresectable colorectal liver metastases with mitoxantrone, 5-fluorouracil, folinic acid, and mitomycin C may prolong survival. | 2001 Dec 1 |
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Synthesis and biological studies of novel nucleoside phosphoramidate prodrugs. | 2001 Dec 6 |
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Coupling of 5-fluoro 2'-deoxyuridine to lactosaminated poly-l-lysine: an approach to a regional, non-invasive chemotherapy of liver micrometastases. | 2001 Feb 15 |
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[Survival of 2 years and 7 months with 5'-DFUR treatment in a patient with peritoneal gastric cancer recurrence]. | 2001 Jan |
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[Effectiveness of high-dose, intermittent 5'-DFUR therapy for advanced gastric cancer]. | 2001 Jan |
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[The efficacy of combination chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR), cyclophosphamide (CPA) and medroxyprogesterone acetate (MPA) for bone metastasis in breast cancer patients]. | 2001 Jul |
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[A phase I study of docetaxel (TXT) and doxifluridine (5'-DFUR) combination therapy in patients with advanced and recurrent breast cancer]. | 2001 Jul |
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Phase I and pharmacologic study of i.v. hydroxyurea infusion given with i.p. 5-fluoro-2'-deoxyuridine and leucovorin. | 2001 Jul |
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Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidine-mediated cell death and cell cycle responses. | 2001 Jul 1 |
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Role of Bax in apoptosis of IL-3-dependent cells. | 2001 Jul 27 |
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Malnutrition and cachexia in ovarian cancer patients: pathophysiology and management. | 2001 Jul-Aug |
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Thymidine phosphorylase expression and effect of doxifluridine: a phase II study. | 2001 Jul-Aug |
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Intracavitary chemotherapy with 5-fluoro-2'-deoxyuridine (FdUrd) in malignant brain tumors. | 2001 Jun |
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Effects of concomitant use of doxifluridine, radiotherapy and immunotherapy in patients with advanced cervical cancer. | 2001 Mar-Apr |
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Sequential intrahepatic and systemic fluoropyrimidine-based chemotherapy for metastatic colorectal cancer confined to the liver. A phase II study. | 2001 May |
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[Hepatic infusion of docetaxel using PEIT for a patient with stage IV breast cancer]. | 2001 Nov |
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Plasma, intestine and tumor levels of 5-fluorouracil in mice bearing L1210 ascites tumor following oral administration of 5-fluorouracil, UFT (mixed compound of tegafur and uracil), carmofur and 5'-deoxy-5-fluorouridine. | 2001 Nov |
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P53 mutation and response to hepatic arterial floxuridine in patients with colorectal liver metastases. | 2001 Nov |
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Acquisition of human concentrative nucleoside transporter 2 (hcnt2) activity by gene transfer confers sensitivity to fluoropyrimidine nucleosides in drug-resistant leukemia cells. | 2001 Nov |
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Fluorodeoxyuridine improves imaging of human glioblastoma xenografts with radiolabeled iododeoxyuridine. | 2001 Nov 1 |
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Combined effects of docetaxel and fluoropyrimidines on tumor growth and expression of interleukin-6 and thymidine phosphorylase in breast cancer xenografts. | 2001 Oct |
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[Effect of peroral doxifluridine plus hepatic arterial infusion for synchronous liver metastasis of colorectal cancer--correlation with the expression of thymidine phosphorylase and dihydropyrimidine dehydrogenase in primary colorectal cancer lesions]. | 2001 Oct |
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[A patient with recurrent breast cancer whose liver metastasis regressed following combined use of weekly docetaxel and MPA.5'-DFUR]. | 2001 Oct |
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Thymidine phosphorylase expression is useful in selecting adjuvant chemotherapy for stage III gastric cancer. | 2001 Oct |
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Docetaxel alone or orally combined with 5-fluorouracil and its derivatives: effects on mouse mammary tumor cell line MM2 in vitro and in vivo. | 2001 Sep |
|
[Combination chemotherapy of doxifluridine plus mitomycin C for colorectal lung metastasis--phase II study]. | 2001 Sep |
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Variations in 5-fluorouracil concentrations of colorectal tissues as compared with dihydropyrimidine dehydrogenase (DPD) enzyme activities and DPD messenger RNA levels. | 2001 Sep |
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Three-dimensional organization of the hepatic microvasculature in hereditary hemorrhagic telangiectasia. | 2001 Sep |
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Inhibition of thymidylate synthase activity by antisense oligodeoxynucleotide and possible role in thymineless treatment. | 2001 Sep |
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A randomized study comparing oral and standard regimens for metastatic breast cancer. | 2001 Sep-Oct |
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Intrahepatic arterial infusion of chemotherapy: pharmacologic principles. | 2002 Apr |
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Downstaging of hepatocellular carcinoma and liver metastases from colorectal cancer by selective intra-arterial chemotherapy. | 2002 Apr |
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[Antimetastatic and antitumor effects of fluoropyrimidines alone and combined with taxanes in a murine model of breast cancer metastatic to the lung]. | 2002 Jan |
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Immunohistochemical variation of human equilibrative nucleoside transporter 1 protein in primary breast cancers. | 2002 Jan |
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Biochemical and molecular effects of UCN-01 in combination with 5-fluorodeoxyuridine in A431 human epidermoid cancer cells. | 2002 Mar |
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Overexpression of pyrimidine nucleoside phosphorylase enhances the sensitivity to 5'-deoxy-5-fluorouridine in tumour cells in vitro and in vivo. | 2002 Mar |
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[Successful treatment of advanced recurent breast cancer using DMpC therapy as maintenance therapy]. | 2002 Mar |
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Systemic irinotecan and regional floxuridine after hepatic cytoreduction in 185 patients with unresectable colorectal cancer metastases. | 2002 Mar |
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Echogenicity of liver metastases from colorectal carcinoma is an independent prognostic factor in patients treated with regional chemotherapy. | 2002 Mar 15 |
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Isolation perfusion of the liver. | 2002 Mar-Apr |
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Percutaneous vs. surgical placement of hepatic artery indwelling catheters for regional chemotherapy. | 2002 Mar-Apr |
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Neoadjuvant chemotherapy with CPT-11 and cisplatin downstages locally advanced gastric cancer. | 2002 Mar-Apr |
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Treatment of patients with superficial bladder cancer by intravesical instillation of anticancer drugs plus oral chemotherapy following TUR-Bt: a randomized controlled trial. | 2002 Mar-Apr |
|
Conjugates of nucleoside analogs with lactosaminated human albumin to selectively increase the drug levels in liver blood: requirements for a regional chemotherapy. | 2002 May |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/floxuridine.html
Usual Adult Dose for Liver Metastasis in Adenocarcinoma
Recommended dose: 0.1 to 0.6 mg/kg/day by continuous arterial infusion; the higher dosage ranges (0.4 mg to 0.6 mg) are usually used for hepatic artery infusion
Route of Administration:
Intra-arterial
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15475457
Coincubation of [3H]-FAU in vitro with 50 nmol/L Floxuridine decreased FAU incorporation into DNA by 70% in HT29 and 84% in LS174T cells
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Classification Tree | Code System | Code | ||
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WHO-ATC |
L01BC09
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NDF-RT |
N0000007770
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NDF-RT |
N0000007770
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NDF-RT |
N0000007770
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NDF-RT |
N0000007770
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LIVERTOX |
NBK548421
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NCI_THESAURUS |
C1557
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NDF-RT |
N0000180853
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NDF-RT |
N0000007770
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FDA ORPHAN DRUG |
195104
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NDF-RT |
N0000007770
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NDF-RT |
N0000007770
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M5414
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039LU44I5M
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50-91-9
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100000081003
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D005467
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60761
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5790
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FLOXURIDINE
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200-072-5
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4801
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039LU44I5M
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1184
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DB00322
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1271008
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2010
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DTXSID3023057
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C504
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3227
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CHEMBL917
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4488
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27640
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SUB07659MIG
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ACTIVE MOIETY
METABOLITE ACTIVE (PRODRUG)
PRODRUG (METABOLITE ACTIVE)