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a salt of phosphoric acid (同)orthophosphate, inorganic_phosphate
carbonated drink with fruit syrup and a little phosphoric acid

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〈U〉リン酸塩 / 《複数形で》リン酸肥料

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/09/23 20:11:17」(JST)

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Fludarabine or fludarabine phosphate (Fludara) is a chemotherapy drug used in the treatment of hematological malignancies (cancers of blood cells such as leukemias and lymphomas). It is a purine analog, which interferes with DNA synthesis.

Indications

Fludarabine is highly effective in the treatment of chronic lymphocytic leukemia, producing higher response rates than alkylating agents such as chlorambucil alone.^[1] Fludarabine is used in various combinations with cyclophosphamide, mitoxantrone, dexamethasone and rituximab in the treatment of indolent non-Hodgkins lymphomas. As part of the FLAG regimen, fludarabine is used together with cytarabine and granulocyte colony-stimulating factor in the treatment of acute myeloid leukaemia. Because of its immunosuppressive effects, fludarabine is also used in some conditioning regimens prior to non myeloablative allogeneic stem cell transplant.

Pharmacology

Fludarabine is a purine analog, and can be given both orally and intravenously. Fludarabine inhibits DNA synthesis by interfering with ribonucleotide reductase and DNA polymerase. It is active against both dividing and resting cells. Being phosphorylated, fludarabine is ionized at physiologic pH and is effectually trapped in blood. This provides some level of specificity for blood cells, both cancerous and healthy.

Side effects

Fludarabine is associated with profound lymphopenia, and as a consequence, increases the risk of opportunistic infections significantly. Patients who have been treated with fludarabine will usually be asked to take co-trimoxazole or to use monthly nebulised pentamidine to prevent Pneumocystis jiroveci pneumonia. The profound lymphopenia caused by fludarabine renders patients susceptible to transfusion-associated graft versus host disease, a fatal complication of blood transfusion. For this reason, all patients who have ever received fludarabine should only be given irradiated blood components.

Fludarabine causes anemia, thrombocytopenia and neutropenia, requiring regular blood count monitoring. Some patients require blood and platelet transfusion, or G-CSF injections to boost neutrophil counts.

Fludarabine is associated with the development of severe autoimmune hemolytic anemia in a proportion of patients.^[2]

Difficulties are often encountered when harvesting peripheral blood stem cells from patients previously treated with fludarabine.^[3]

History

Fludarabine was produced by John Montgomery and Kathleen Hewson of the Southern Research Institute in 1968.^[4] Their previous work involved 2-fluoroadenosine, which was unsafe for use in humans; the change to this arabinose analogue was inspired by the success of vidarabine.^[4]

References

^ Rai KR et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 2000;343:1750-7. doi:10.1056/NEJM200012143432402 PMID 11114313
^ Gonzalez H et al. Severe autoimmune hemolytic anemia in eight patients treated with fludarabine. Hematol Cell Ther. 1998;40:113-8. PMID 9698219
^ Tournilhac O et al. Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood 2004;103:363-5. PMID 12969985
^ ^a ^b Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. pp. 258. ISBN 0-471-89979-8.

External links

Fludara webpage

UpToDate Contents

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1. 症候性または進行した慢性リンパ性白血病に対する初期治療の選択 selection of initial therapy for symptomatic or advanced chronic lymphocytic leukemia
2. リンパ腫のプロトコル protocols for lymphoma
3. 進行期（III/IV）濾胞性リンパ腫の初期治療 initial treatment of advanced stage iii iv follicular lymphoma
4. 血液悪性腫瘍を有する成人における侵襲性真菌感染症予防 prophylaxis of invasive fungal infections in adults with hematologic malignancies
5. 再発性または難治性のマントル細胞リンパ腫の治療 treatment of relapsed or refractory mantle cell lymphoma

English Journal

Phospholipid derivatives of cladribine and fludarabine: Synthesis and biological properties.

Tsybulskaya I1, Kulak T2, Kalinichenko E2, Baranovsky A2, Bogushevich S2, Golubeva M2, Kuzmitsky B2.
Bioorganic & medicinal chemistry.Bioorg Med Chem.2015 Jul 1;23(13):3287-96. doi: 10.1016/j.bmc.2015.04.059. Epub 2015 Apr 25.
Phospholipid derivatives of anticancer nucleosides cladribine and fludarabine (F-ara-A) bearing 1,2- and 1,3-diacylglycerol moieties have been prepared by the H-phosphonate approach using 1,1,3,3-tetraisopropyldisiloxane-1,3-diyl protecting group for cladribine and a combination of tert-butyldimethy
PMID 25960323

Apoptosis-induced activation of HIV-1 in latently infected cell lines.

Khan SZ1, Hand N2, Zeichner SL3,4,5.
Retrovirology.Retrovirology.2015 May 16;12:42. doi: 10.1186/s12977-015-0169-1.
BACKGROUND: Despite much work, safe and effective approaches to attack and deplete the long-lived reservoir of cells latently infected with HIV-1 remain an elusive goal. Patients infected with HIV-1 treated with cytotoxic agents or bone marrow transplantation can experience decreases in the reservoi
PMID 25980942

Population pharmacokinetic/dynamic model of lymphosuppression after fludarabine administration.

McCune JS1, Vicini P, Salinger DH, O'Donnell PV, Sandmaier BM, Anasetti C, Mager DE.
Cancer chemotherapy and pharmacology.Cancer Chemother Pharmacol.2015 Jan;75(1):67-75. doi: 10.1007/s00280-014-2618-2. Epub 2014 Nov 6.
PURPOSE: Quantitative relationships between 9-β-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) concentrations and lymphosuppression have not been reported, but would be useful for regimen design. A population pharmacokinetic/pharmacodynamic model was constructed in this study using data from 41 hemat
PMID 25374408

Japanese Journal

Industrial Info. 慢性リンパ性白血病(CLL)に対するフルダラビンリン酸エステル(フルダラ)

鬼頭将仁
細胞 42(14), 606-609, 2010-12
NAID 40018744080

フルダラビンの新規蛍光測定法の開発およびATL患者におけるジドブジンの血中動態解析

上野順也
福岡大学薬学集報 9(0), 163-164, 2009-03
NAID 110007040153

再発・難治低悪性度B細胞リンパ腫に対する経口フルダラビンの国内臨床試験と薬物動態 (特集 RI標識抗CD20抗体と経口フルダラビンの国内承認とB細胞リンパ腫治療)

小川吉明
血液・腫瘍科 56(1), 32-38, 2008-01
NAID 40019063523

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★リンクテーブル★

リンク元	「フルダラビン」「FLUDARA」
関連記事	「phosphate」

「フルダラビン」

Fludarabine
Systematic (IUPAC) name
	[(2R,3R,4S,5R)-5-(6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl]methoxyphosphonic acid
Clinical data
Trade names	Fludara
AHFS/Drugs.com	monograph
MedlinePlus	a692003
Pregnancy cat.	D
Legal status	Prescription Only (S4) (AU) POM (UK)
Routes	Intravenous, oral
Pharmacokinetic data
Bioavailability	55%
Protein binding	19 to 29%
Half-life	20 hours
Excretion	Renal
Identifiers
CAS number	75607-67-9
ATC code	L01BB05
PubChem	CID 657237
DrugBank	DB01073
ChemSpider	571392
UNII	P2K93U8740
KEGG	D01907
ChEMBL	CHEMBL1568
Chemical data
Formula	C10H13FN5O7P
Mol. mass	365.212 g/mol
	SMILES Fc1nc(c2ncn(c2n1)[C@@H]3O[C@@H]([C@@H](O)[C@@H]3O)CO)N;
	InChI InChI=1S/C10H12FN5O4/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(19)5(18)3(1-17)20-9/h2-3,5-6,9,17-19H,1H2,(H2,12,14,15)/t3-,5-,6+,9-/m1/s1 ; Key:HBUBKKRHXORPQB-FJFJXFQQSA-N ;
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