シタラビン、シトシンアラビノシド、アラビノフラノシルシトシン

関: arabinofuranosylcytosine、cytarabine、cytarabine hydrochloride、cytarabine ocfosphate、cytosine arabinoside

関: Cytarabine

WordNet

the 3rd letter of the Roman alphabet (同)c
(music) the keynote of the scale of C major
a general-purpose programing language closely associated with the UNIX operating system
macaws (同)genus Ara
a constellation in the southern hemisphere near Telescopium and Norma

PrepTutorEJDIC

carbonの化学記号
cesiumの化学記号
cadmiumの化学記号
are (面積の単位)の変形

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/07/29 12:53:39」(JST)

wiki ja

[Wiki ja表示]

シタラビン (Cytarabine) とは、抗悪性腫瘍剤（抗がん剤）の一種。商品名はキロサイド（Cylocide）。

Ara-CまたはAraCという略号で表されることがある。核酸の誘導体である。

効能・効果

急性白血病（赤白血病、慢性骨髄性白血病の急性転化例を含む）。
消化器癌（胃癌、胆嚢癌、胆道癌、膵癌、肝癌、結腸癌、直腸癌等）、肺癌、乳癌、女性性器癌（子宮癌、卵巣癌等）等。
- ただし他の抗腫瘍剤と併用する場合に限る。
膀胱腫瘍
シタラビン大量療法（相当のリスクのある治療法）
- 再発又は難治性の下記疾患
- 急性白血病（急性骨髄性白血病、急性リンパ性白血病）
- 悪性リンパ腫
- ただし、急性リンパ性白血病及び悪性リンパ腫については他の抗腫瘍剤と併用する場合に限る。

上記のように効能・効果は多数あるが、実際には血液がん中心に使われる。

副作用

骨髄抑制、ショック、シタラビン症候群、急性呼吸窮迫症候群、間質性肺炎、高ビリルビン血症を伴う肝障害、不整脈、心不全､消化管潰瘍や出血や好中球減少性腸炎等の消化管障害､可逆的な言語障害や運動失調や傾眠や昏睡や白質脳症等の中枢神経系障害、肝膿瘍、急性膵炎、肺浮腫、有痛性紅斑、脱毛（症）、発疹、頭痛、活動低下、傾眠、言語障害、食欲不振、嘔気、嘔吐、下痢、ALT (GPT) 上昇、AST (GOT) 上昇、LDH上昇、ビリルビン上昇、肝機能異常、Al-P上昇、γ-GTP上昇、電解質異常、血中尿酸上昇・低下、電解質代謝異常、フィブリノーゲン増加、凝固時間延長・短縮、FDP増加、BUN上昇・低下、尿糖陽性、クレアチニン上昇、尿蛋白陽性、低蛋白血症、結膜炎、体重増加・減少、CK上昇・低下、感染、敗血症、ウロビリノーゲン陽性など多数ある。

作用機序

DNAの合成過程において、CDPレダクターゼおよびDNAポリメラーゼを阻害する。また、白血病細胞の分化を誘導する^[1]。

脚注

^ 医薬品インタビューフォーム-キロサイド注 (PDF) （日本新薬）

この項目は、薬学に関連した書きかけの項目です。この項目を加筆・訂正などしてくださる協力者を求めています（プロジェクト:薬学／Portal:医学と医療）。

wiki en

[Wiki en表示]

Cytarabine, also known as cytosine arabinoside (ara-C), is a chemotherapy medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma. It is given by injection into a vein, under the skin, or into the cerebrospinal fluid. There is a liposomal formulation for which there is tentative evidence of better outcomes in lymphoma involving the meninges.^[1]

Common side effects include bone marrow suppression, vomiting, diarrhea, liver problems, rash, ulcer formation in the mouth, and bleeding. Other serious side effects include loss of consciousness, lung disease, and allergic reactions. Use during pregnancy may harm the baby.^[1] Cytarabine is in the antimetabolite and nucleoside analog families of medication.^[2] It works by blocking the function of DNA polymerase.^[1]

Cytarabine was patented in 1960 and approved for medical use in 1969.^[3] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.^[4] The wholesale cost in the developing world is about 4.27 to 5.7 USD per 500 mg vial.^[5] This dose in the United Kingdom costs the NHS about 50.00 pounds while the liposomal form is 1,223.75 pounds per 50 mg vial.^[2]

Medical uses

Cytarabine is mainly used in the treatment of acute myeloid leukaemia, acute lymphocytic leukaemia (ALL) and in lymphomas,^[6] where it is the backbone of induction chemotherapy.

Cytarabine also possesses antiviral activity, and it has been used for the treatment of generalised herpesvirus infection. However, cytarabine is not very selective in this setting and causes bone marrow suppression and other severe side effects. Therefore, ara-C is not a useful antiviral agent in humans because of its toxic profile^[7] and actually it is used mainly for the chemotherapy of hematologic cancers.

Cytarabine is also used in the study of the nervous system to control the proliferation of glial cells in cultures, the amount of glial cells having an important impact on neurons.^{[citation needed]}

Side effects

One of the unique toxicities of cytarabine is cerebellar toxicity when given in high doses, which may lead to ataxia. Cytarabine may cause granulocytopenia and other impaired body defenses, which may lead to infection, and thrombocytopenia, which may lead to hemorrhage.

Toxicity: leukopenia, thrombocytopenia, anemia, GI disturbances, stomatitis, conjunctivitis, pneumonitis, fever, and dermatitis, palmar-plantar erythrodysesthesia. Rarely, myelopathy has been reported after high dose or frequent intrathecal Ara-C administration.^[8]

When used in protocols designated as high dose, cytarabine can cause cerebral and cerebellar dysfunction, ocular toxicity, pulmonary toxicity, severe GI ulceration and peripheral neuropathy (rare).

To prevent the side effects and improve the therapeutic efficiency, various derivatives of these drugs (including amino acid, peptide, fatty acid and phosphates) have been evaluated, as well as different delivery systems.^[9]

Mechanism of action

Cytosine arabinoside combines a cytosine base with an arabinose sugar. It is an antimetabolic agent with the chemical name of 1β-arabinofuranosylcytosine. Certain sponges, where it was originally found, use arabinoside sugars to form a different compound (not part of DNA). Cytosine arabinoside is similar enough to human cytosine deoxyribose (deoxycytidine) to be incorporated into human DNA, but different enough that it kills the cell. Cytosine arabinoside interferes with the synthesis of DNA. Its mode of action is due to its rapid conversion into cytosine arabinoside triphosphate, which damages DNA when the cell cycle holds in the S phase (synthesis of DNA). Rapidly dividing cells, which require DNA replication for mitosis, are therefore most affected. Cytosine arabinoside also inhibits both DNA^[10] and RNA polymerases and nucleotide reductase enzymes needed for DNA synthesis. Cytarabine is the first of a series of cancer drugs that altered the sugar component of nucleosides. Other cancer drugs modify the base.^[11]

Cytarabine is often given by continuous intravenous infusion, which follows a biphasic elimination – initial fast clearance rate followed by a slower rate of the analog.^[12] Cytarabine is transported into the cell primarily by hENT-1.^[13] It is then monophosphorylated by deoxycytidine kinase and eventually cytarabine-5´-triphosphate, which is the active metabolite being incorporated into DNA during DNA synthesis.

Several mechanisms of resistance have been reported.^[14] Cytarabine is rapidly deaminated by cytidine deaminase in the serum into the inactive uracil derivative. Cytarabine-5´-monophosphate is deaminated by deoxycytidylate deaminase, leading to the inactive uridine-5´-monophosphate analog.^[15] Cytarabine-5´-triphosphate is a substrate for SAMDH1.^[16] Furthermore, SAMHD1 has ben shown to limit the efficacy of cytarabine efficacy in patients.^[17]

When used as an antiviral, cytarabine-5´-triphosphate functions by inhibiting viral DNA synthesis.^[18] Cytarabine is able to inhibit herpesvirus and vaccinia virus replication in cells during tissue culture. However, cytarabine treatment was only effective for herpesvirus infection in a murine model.

History

Cytarabine was first synthesized in 1959 by Richard Walwick, Walden Roberts, and Charles Dekker at the University of California, Berkeley.^[19]

It was approved by the United States Food and Drug Administration in June 1969, and was initially marketed in the U.S. by Upjohn under the trade name Cytosar-U.

Names

It is also known as ara-C (arabinofuranosyl cytidine).^[20]

Cytosar-U
Tarabine PFS (Pfizer)
Depocyt (longer-lasting liposomal formulation)
AraC

References

^ ^a ^b ^c "Cytarabine". The American Society of Health-System Pharmacists. Retrieved 8 December 2016.
^ ^a ^b British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 589. ISBN 9780857111562.
^ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 511. ISBN 9783527607495.
^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016.
^ "Cytarabine". International Drug Price Indicator Guide. Retrieved 8 December 2016.
^ Pigneux A, Perreau V, Jourdan E, et al. (October 2007). "Adding lomustine to idarubicin and cytarabine for induction chemotherapy in older patients with acute myeloid leukemia: the BGMT 95 trial results". Haematologica. 92 (10): 1327–34. PMID 18024370. doi:10.3324/haematol.11068.
^ Lauter, CB.; Bailey, EJ.; Lerner, AM. (Nov 1974). "Assessment of cytosine arabinoside as an antiviral agent in humans.". Antimicrob Agents Chemother. 6 (5): 598–602. PMC 444699 . PMID 15825312. doi:10.1128/aac.6.5.598.
^ Watterson J, Toogood I, Nieder M, et al. (December 1994). "Excessive spinal cord toxicity from intensive central nervous system-directed therapies". Cancer. 74 (11): 3034–41. PMID 7954266. doi:10.1002/1097-0142(19941201)74:11<3034::AID-CNCR2820741122>3.0.CO;2-O.
^ Chhikara BS, Parang K (2010). "Development of cytarabine prodrugs and delivery systems for leukemia treatment". Expert Opinion on Drug Delivery. 7 (12): 1399–1414. doi:10.1517/17425247.2010.527330.
^ Perry, Michael J. (2008). The Chemotherapy source book. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 80. ISBN 0-7817-7328-8.
^ Feist, Patty (April 2005). "A Tale from the Sea to Ara C".
^ Liliemark JO, Gahrton G, Paul CY, Peterson CO (Jun 1987). "ara-C in plasma and ara-CTP in leukemic cells after subcutaneous injection and continuous intravenous infusion of ara-C in patients with acute nonlymphoblastic leukemia". Semin Oncol. 14 (2 (Suppl 1)): 167–71. PMID 3589691.
^ Clarke ML, Mackey JR, Baldwin SA, Young JD, Cass CE (2002). "The role of membrane transporters in cellular resistance to anticancer nucleoside drugs". Cancer Treat Res. 112: 27–47. PMID 12481710.
^ Shelton J, Lu X, Hollenbaugh JA, Cho JH, Amblard F, Schinazi RF (Dec 2016). "Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs". Chem Rev. 116 (23): 14379–14455. PMID 27960273. doi:10.1021/acs.chemrev.6b00209.
^ Drake JC, Hande KR, Fuller RW, Chabner BA (Mar 1980). "Cytidine and deoxycytidylate deaminase inhibition by uridine analogs". Biochem Pharmacol. 29 (5): 807–11. PMID 20227960. doi:10.1016/0006-2952(80)90561-4.
^ Hollenbaugh JA, Shelton J, Tao S, Amiralaei S, Liu P, Lu X, Goetze RW, Zhou L, Nettles JH, Schinazi RF, Kim B (Jan 2017). "Substrates and Inhibitors of SAMHD1". PLOS ONE. 12 (1): e0169052. PMC 5207538 . PMID 28046007. doi:10.1371/journal.pone.0169052.
^ Schneider C, Oellerich T, Baldauf HM, Schwarz SM, Thomas D, Flick R, Bohnenberger H, Kaderali L, Stegmann L, Cremer A, Martin M, Lohmeyer J, Michaelis M, Hornung V, Schliemann C, Berdel WE, Hartmann W, Wardelmann E, Comoglio F, Hansmann ML, Yakunin AF, Geisslinger G, Ströbel P, Ferreirós N, Serve H, Keppler OT, Cinatl J Jr (Dec 2016). "SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia". Nat Med. 23: 250–255. PMID 27991919. doi:10.1038/nm.4255.
^ Lemke, Thomas L.; Williams, David H.; Foye, William O. (2002). Foye's principles of medicinal chemistry. Hagerstwon, MD: Lippincott Williams & Wilkins. p. 963. ISBN 0-683-30737-1.
^ Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. p. 258. ISBN 0-471-89979-8.
^ Ogbomo H, Michaelis M, Klassert D, Doerr HW, Cinatl J (December 2008). "Resistance to cytarabine induces the up-regulation of NKG2D ligands and enhances natural killer cell lysis of leukemic cells". Neoplasia. 10 (12): 1402–10. PMC 2586691 . PMID 19048119. ^{[permanent dead link]}

External links

MedlinePlus page on cytarabine
ADAP drugs page on cytarabine
BC Cancer network page on cytarabine
Chembank entry

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 非プラチナ製剤ベースの癌化学療法の神経学的合併症の概要 overview of neurologic complications of non platinum cancer chemotherapy
2. 若年成人における急性骨髄性白血病に対する導入療法 induction therapy for acute myeloid leukemia in younger adults
3. 高齢者における急性骨髄性白血病の治療 treatment of acute myeloid leukemia in older adults
4. 軟髄膜転移の治療（癌性髄膜炎） treatment of leptomeningeal metastases carcinomatous meningitis
5. 全身化学療法に対する輸注反応 infusion reactions to systemic chemotherapy

English Journal

Hypoxia influences stem cell-like properties in multidrug resistant K562 leukemic cells.

Cui XY, Skretting G, Jing Y, Sun H, Sandset PM, Sun L.SourceDepartment of Hematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Stem Cell Research Center, Zhengzhou University, Zhengzhou, China; Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway. Electronic address: x.y.cui@medisin.uio.no.
Blood cells, molecules & diseases.Blood Cells Mol Dis.2013 Oct;51(3):177-84. doi: 10.1016/j.bcmd.2013.05.003. Epub 2013 May 29.
OBJECTIVES: The present study investigates the potential role of hypoxia in maintaining stem cell-like properties and therapeutic resistance in K562 leukemic cell.METHODS: Western blot, flow cytometry and cell viability assays were used to investigate the effects of hypoxia (1% O2) on cell prolifera
PMID 23725749

Optimization of cytarabine (ARA-C) therapy for acute myeloid leukemia.

Momparler RL.AbstractCytarabine (cytosine arabinoside) is one of the most effective drugs for the treatment of acute myeloid leukemia. The standard dose of cytarabine used to treat this leukemia is 100 mg per square meter. In an attempt to improve the effectiveness of cytarabine against acute myeloid leukemia, a high-dose treatment (3,000 mg per square meter) was introduced into therapy. The side effects of high-dose cytarabine was a major concern, especially its neurological toxicity. A review of recent clinical trials indicates that this high-dose cytarabine can be replaced by the intermediate-dose of 1,000 mg per square meter without loss of efficacy and with less toxicity. This is an important step to improve the efficacy of cytarabine for the treatment of acute myeloid leukemia. Despite the improvements in the therapy for this leukemia, the current overall survival rate for adult patients is less than 30%. To optimize the cytarabine therapy, it is important to determine how some leukemic stem cells survive treatment. Preclinical data suggest that survival of the leukemic stem cells could be due to the long 12 hour interval between infusions of cytarabine, which permits some leukemic cells to escape its S phase specific action. Among the other factors that can lead to leukemic cell survival are the high levels in the liver and spleen of cytidine deaminase, the enzyme that inactivates cytarabine and drug resistance due to deficiency in deoxycytidine kinase, the enzyme that activates the prodrug, cytarabine. Several approaches are proposed in this commentary to overcome these impediments with the goal of increasing the effectiveness of cytarabine for the treatment of acute myeloid leukemia.
Experimental hematology & oncology.Exp Hematol Oncol.2013 Aug 6;2(1):20. [Epub ahead of print]
Cytarabine (cytosine arabinoside) is one of the most effective drugs for the treatment of acute myeloid leukemia. The standard dose of cytarabine used to treat this leukemia is 100 mg per square meter. In an attempt to improve the effectiveness of cytarabine against acute myeloid leukemia, a high-do
PMID 23919448

Association between baseline body mass index and overall survival among patients over age 60 with acute myeloid leukemia.

Brunner AM, Sadrzadeh H, Feng Y, Drapkin BJ, Ballen KK, Attar EC, Amrein PC, McAfee SL, Chen YB, Neuberg DS, Fathi AT.SourceDepartment of Hematology and Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts.
American journal of hematology.Am J Hematol.2013 Aug;88(8):642-6. doi: 10.1002/ajh.23462. Epub 2013 May 30.
Acute myeloid leukemia (AML) is more common and more lethal among patients over the age of 60. Increased body mass index (BMI) has been associated with a higher incidence of various malignancies, including AML. We sought to determine whether patient BMI at the time of AML diagnosis is related to ove
PMID 23619915

Japanese Journal

Efficacy of Intrathecal MTX/Ara-C Combined with Systemic Chemotherapy in a Gastric Cancer Patient with Meningeal Carcinomatosis

Internal Medicine 55(6), 609-611, 2016
NAID 130005138081

Characters of Frontier Orbitals of Antiviral Drugs

滋賀大学教育学部紀要 (64), 141-144, 2015-03-31
NAID 120005596768

Effects of Decitabine on Invasion and Exosomal Expression of miR-200c and miR-141 in Oxaliplatin-Resistant Colorectal Cancer Cells

Biological and Pharmaceutical Bulletin 38(9), 1272-1279, 2015
NAID 130005096996

Related Pictures

★リンクテーブル★

リンク元	「シタラビン」「cytarabine hydrochloride」「シトシンアラビノシド」「アラビノフラノシルシトシン」「arabinofuranosylcytosine」
関連記事	「C」「Cs」「Cd」「c」

「シタラビン」

Cytarabine
Clinical data
Trade names	Cytosar-U, Depocyt, others
AHFS/Drugs.com	Monograph
MedlinePlus	a682222
Pregnancy; category	AU: D; US: D (Evidence of risk); ;
Routes of; administration	injectable (intravenous injection or infusion, intrathecal, or subcutaneously)
ATC code	L01BC01 (WHO);
Legal status
Legal status	In general: ℞ (Prescription only);
Pharmacokinetic data
Bioavailability	20% by mouth
Protein binding	13%
Metabolism	liver
Biological half-life	biphasic: 10 min, 1–3 hr
Excretion	kidney
Identifiers
	IUPAC name 4-amino-1-[(2R,3S,4R,5R)-3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl] pyrimidin-2-one;
CAS Number	147-94-4 ;
PubChem CID	6253;
IUPHAR/BPS	4827;
DrugBank	DB00987 ;
ChemSpider	6017 ;
UNII	04079A1RDZ;
KEGG	D00168 ;
ChEBI	CHEBI:28680 ;
ChEMBL	CHEMBL803 ;
PDB ligand	AR3 (PDBe, RCSB PDB);
ECHA InfoCard	100.005.188
Chemical and physical data
Formula	C9H13N3O5
Molar mass	243.217 g/mol
3D model (JSmol)	Interactive image;
	SMILES O=C1/N=C(/N)\C=C/N1[C@@H]2O[C@@H]([C@@H](O)[C@@H]2O)CO ;
	InChI InChI=1S/C9H13N3O5/c10-5-1-2-12(9(16)11-5)8-7(15)6(14)4(3-13)17-8/h1-2,4,6-8,13-15H,3H2,(H2,10,11,16)/t4-,6-,7+,8-/m1/s1 ; Key:UHDGCWIWMRVCDJ-CCXZUQQUSA-N ;
(verify)