| Identification | More | [Name]
Fludarabine phosphate | [CAS]
75607-67-9 | [Synonyms]
9-bata-d-arabinofuranosyl-2-fluoroadenine phosphate
9-BETA-D-ARABINOFURANOSYL-2-FLUOROADENINE-5'-DIHYDROGEN PHOSPHATE
FLUDARABINE PHOSPHATE
FLUDARUBINE PHOSPHATE
2-fluoro-9-(5-o-phosphono-beta-d-arabinofuranosyl)-9h-purin-6-amin
2-fluoro-9-(5-o-phosphono-beta-d-arabinofuranosyl)-9h-purin-6-amine
2-fluoro-araamp
9-beta-arabinofuranosyl-2-fluoroadenine-5’-phosphate
9-beta-d-arabinofuranosyl-2-fluoroadenine5’-monophosphate
fludarabinemonophosphate
FludarabinePhosphateFdaInspected
FludarabinePhosphateUsp28
fludarabine hcl
9-BETA-D-ARABINOFURANOSYL-2-FLUOROADENINE PHOSPHATE
Fludarabin Phosphate
((2R,3S,4S,5R)-5-(6-AMINO-2-FLUORO-9H-PURIN-9-YL)-3,4-DIHYDROXYTETRAHYDROFURAN-2-YL)METHYL DIHYDROGEN PHOSPHATE
FLUDARABINE PHOSPHATE (FLUDARABINE 5''-MONOPHOSPHATE)
2-Fluoro-9-(5-O-phosphono-β-D-arabinofuranosyl)-9H-purin-6-amine
9-(5-O-Phosphono-β-D-arabinofuranosyl)-2-fluoro-9H-purine-6-amine
F-ara-AMP | [EINECS(EC#)]
616-242-0 | [Molecular Formula]
C10H13FN5O7P | [MDL Number]
MFCD00866418 | [Molecular Weight]
365.21 | [MOL File]
75607-67-9.mol |
| Chemical Properties | Back Directory | [Appearance]
White or almost white, crystalline powder, hygroscopic. | [Melting point ]
203°C(dec.)(lit.) | [alpha ]
[α]D20 +10～+14゜(c=0.5,H2O) | [Boiling point ]
864.2±75.0 °C(Predicted) | [density ]
2.39±0.1 g/cm3(Predicted) | [RTECS ]
UO7440900 | [storage temp. ]
2-8°C | [solubility ]
DMSO: soluble1mg/mL | [form ]
Powder | [pka]
1.86±0.10(Predicted) | [color ]
white | [Water Solubility ]
Soluble in DMSO or water at 5mg/ml | [Merck ]
14,4126 | [Stability:]
Hygroscopic | [InChIKey]
GIUYCYHIANZCFB-GFRUICAKSA-N | [CAS DataBase Reference]
75607-67-9(CAS DataBase Reference) |
| Hazard Information | Back Directory | [Description]
Fludarabine phosphate is an antimetabolite indicated for the treatment of B cell
lymphocytic leukemia. It is reportedly effective in patients refractory to other
therapies. Fludarabine phosphate acts by inhibiting primer RNA synthesis. Its side
effects include bone marrow suppression, anemia, thrombocytopenia and neutropenia. | [Chemical Properties]
White or almost white, crystalline powder, hygroscopic. | [Originator]
Southern Research Institute (U.S.A.) | [Uses]
anticonvulsant | [Definition]
ChEBI: A purine arabinonucleoside monophosphate having 2-fluoroadenine as the nucleobase. A prodrug, it is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. Onc
incorporated into DNA, 2-fluoro-ara-ATP functions as a DNA chain terminator. It is used for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to, or whose disease has progressed during, treatment with at
least one standard alkylating-agent containing regimenas. | [Brand name]
Fludara (Berlex). | [Mechanism of action]
Fludarabine phosphate is a cytotoxic purine antimetabolite that acts by inhibiting DNA synthesis. Fludarabine and its
soluble derivatives interfere with phosphorylation, e.g., in L 1210 cells. Fludarabine behaves more like an analog of deoxycytidine
than adenine or deoxyadenine as indicated by
reports demonstrating that the presence of
fluorine in the 2-position of the adenine ring alters its function as a substrate for deaminase and
nucleoside kinases. This results in differences
in biological activity and metabolism. Halogenation does not simply block deamination,
but also influences the enzyme that carries out
the phosphorylation, as a result cytotoxicity is
increased. Fludarabine phosphate may selectively inhibit the incorporation of thymidine
and uridine into the DNA molecule by inhibiting
both ribonucleotide reductase and DNA
polymerase. The maximum tolerated dose
(MTD) in heavily pretreated patients with advanced malignancy/solid tumors on the daily
regimen was about 15 mg/m2. Granulocytopenia and thrombocytopenia were dose-limiting. | [Pharmacology]
Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.
Phase I studies in humans have demonstrated that fludarabine phosphate is rapidly converted to the active metabolite, 2-fluoro-ara-A, within minutes after intravenous infusion.
Consequently, clinical pharmacology studies have focused on 2-fluoro-ara-A pharmacokinetics. After the five daily doses of 25 mg 2-fluoro-ara-AMP/m2 to cancer patients infused over 30 minutes, 2-fluoro-ara-A concentrations show a moderate accumulation. During a 5-day treatment schedule, 2-fluoro-ara-A plasma trough levels increased by a factor of about 2. The terminal half-life of 2-fluoro-ara-A was estimated as approximately 20 hours. In vitro, plasma protein binding of fludarabine ranged between 19% and 29%. | [Clinical Use]
Fludarabine phosphate (Fludara ® ), is a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-β-D-arabinofuranosyladenine(ara-A), which differs only by the presence of a fluorine atom at position 2 of the purine moiety and a phosphate group at position 5 of the arabinose moiety (Plunkett et al., 1993). These structural modifications result in increased aqueous solubility and resistance to enzymatic degradation by adenosine deaminases compared to vidarabine (Brockman et al., 1977; Plunkett et al., 1990). Fludarabine phosphate is indicated for the treatment of patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating agent containing regimen (Boogaerts et al., 2001; Rossi et al., 2004). | [target]
DNA synthesis | [Drug interactions]
Potentially hazardous interactions with other drugs
Antipsychotics: avoid concomitant use with
clozapine, increased risk of agranulocytosis.
Cytotoxics: increased pulmonary toxicity with
pentostatin (unacceptably high incidence of
fatalities); increases intracellular concentration of
cytarabine. | [Metabolism]
Intravenous fludarabine phosphate is rapidly
dephosphorylated to fludarabine which is taken up
by lymphocytes and rephosphorylated via the enzyme
deoxycytidine kinase to the active triphosphate
nucleotide. Clearance of fludarabine from the plasma
is triphasic; elimination is mostly via renal excretion:
40-60% of an intravenous dose is excreted in the urine.
The pharmacokinetics of fludarabine show considerable
inter-individual variation |
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