Cytarabine Systematic (IUPAC) name 4-amino-1-[(2R,3S,4R,5R)-3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl] pyrimidin-2-one Clinical data AHFS/Drugs.com MedlinePlus Pregnancy cat. D (USA); D (Aus) Legal status ? Routes Injectable (intravenous injection or infusion, intrathecal, or subcutaneously) Pharmacokinetic data Bioavailability 20% oral Protein binding 13% Metabolism Liver Half-life biphasic: 10 min, 1-3 hr Excretion Renal Identifiers CAS number ATC code L01 PubChem DrugBank ChemSpider UNII KEGG ChEBI ChEMBL Chemical data Formula C9H13N3O5 Mol. mass 243.217 g/mol SMILES & (what is this?)
Cytarabine, or cytosine arabinoside, is a chemotherapy agent used mainly in the treatment of cancers of white blood cells such as acute myeloid leukemia (AML) and non-Hodgkin lymphoma. It is also known as Ara-C (Arabinofuranosyl Cytidine). It destroys cancer cells by interfering with DNA synthesis.
It is called cytosine arabinoside because it combines a cytosine base with an arabinose sugar. Cytosine normally combines with a different sugar, deoxyribose, to form deoxycytidine, a component of DNA. 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. This mechanism is used to kill cancer cells. Cytarabine is the first of a series of cancer drugs that altered the sugar component of nucleosides. Other cancer drugs modify the base.
Cytosine arabinoside interferes with the synthesis of DNA. It is an antimetabolic agent with the chemical name of 1β-arabinofuranosylcytosine. 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 and RNA polymerases and nucleotide reductase enzymes needed for DNA synthesis.
Cytarabine is rapidly deaminated in the body into the inactive uracil derivative and therefore is often given by continuous intravenous infusion.
Orally, less than 20% of a dose of cytarabine is absorbed from the gastrointestinal tract and is ineffective by this route. Subcutaneously or intramuscularly, tritium-labelled cytarabine produces peak plasma concentrations of radioactivity within 20 to 60 minutes which are considerably lower than those attained after intravenous administration. Continuous intravenous infusions produce relatively constant plasma levels in 8 to 24 hours.
Intravenous doses of cytarabine exhibit a biphasic elimination, with an initial distribution half-life of about ten minutes during which time a major portion of the drug is metabolised in the liver to the inactive metabolite uracil arabinoside. The secondary elimination half-life is longer, approximately one to three hours. Metabolism also occurs in the kidneys, gastrointestinal mucosa, granulocytes and other tissues.
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, so it is used mainly for the chemotherapy of hematologic cancers.
One of the unique toxicities of cytarabine is cerebellar toxicity when given in high doses.
Possible infection resulting from granulocytopenia and other impaired body defences, and hemorrhage secondary to thrombocytopenia
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.
- Tarabine PFS (Pfizer)
- Depocyt (longer-lasting liposomal formulation)
- ^ Wang WS, Tzeng CH, Chiou TJ, et al. (June 1997). "High-dose cytarabine and mitoxantrone as salvage therapy for refractory non-Hodgkin's lymphoma" ([dead link]). Jpn. J. Clin. Oncol. 27 (3): 154–7. doi:10.1093/jjco/27.3.154. PMID 9255269. http://jjco.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9255269.
- ^ 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. http://www.neoplasia.com/abstract.php?msid=1944.
- ^ Feist, Patty (April 2005). "A Tale from the Sea to Ara C". http://www.pfeist.net/ALL/arac/.
- ^ Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. p. 258. ISBN 0-471-89979-8.
- ^ Perry, Michael J. (2008). The Chemotherapy source book. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 80. ISBN 0-7817-7328-8.
- ^ Lemke, Thomas L.; Williams, David H.; Foye, William O. (2002). Foye's principles of medicinal chemistry. Hagerstwon, MD: Lippincott Williams & Wilkins. pp. 963. ISBN 0-683-30737-1.
- ^ 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. doi:10.3324/haematol.11068. PMID 18024370. http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=18024370.
- ^ 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. doi:10.1002/1097-0142(19941201)74:11<3034::AID-CNCR2820741122>3.0.CO;2-O. PMID 7954266.
- MedlinePlus page on cytarabine
- ADAP drugs page on cytarabine
- BC Cancer network page on cytarabine
- Chembank entry
- Sea to Ara C An essay on the history of cytarabine.
Intracellular chemotherapeutic agents/antineoplastic agents (L01) SPs/MIs
(M phase)Block microtubule assemblyBlock microtubule disassembly
inhibitorIIICrosslinking of DNA
(CCNS)Aziridines: Carboquone • ThioTEPA • Triaziquone • Triethylenemelamine
Photosensitizers/PDT OtherOther/ungroupedAmsacrine • Trabectedin • retinoids (Alitretinoin, Tretinoin) • Arsenic trioxide • asparagine depleters (Asparaginase/Pegaspargase) • Celecoxib • Demecolcine • Elesclomol • Elsamitrucin • Etoglucid • Lonidamine • HAMLET (human alpha-lactalbumin made lethal to tumor cells) • Lucanthone • Mitoguazone • Mitotane • Oblimersen • Omacetaxine mepesuccinate • mTOR inhibitors (Everolimus, Temsirolimus)
tumr, epon, para
DNA virus antivirals (primarily J05, also S01AD and D06BB) Baltimore IDNA-synthesis
inhibitorTK activatedNot TK activatedOther
Hepatitis B (VII) Multiple/generalNucleic acid inhibitorsMultiple/unknownErbB2/PI3K PathwayNOV-205§ • NOV-002†
Wikimedia Foundation. 2010.
Look at other dictionaries:
Cytarabine — Structure chimique de l arabinoside de cytosine Général Nom IUPAC 1β arabinofuranosylcytosine … Wikipédia en Français
cytarabine — /suy tar euh been /, n. Pharm. a toxic synthetic nucleoside, C9H13N3O5, used as an immunosuppressive and cytotoxic agent in the treatment of certain leukemias. Also cytosine arabinoside, ara C. [CYT(OSINE) + ARAB(INOSIDE) + INE2] * * * … Universalium
cytarabine — noun A particular drug used in chemotherapy. Syn: cytosine arabinoside … Wiktionary
cytarabine — SYN: arabinosylcytosine. * * * cyt·ar·a·bine sīt ar ə .bēn n CYTOSINE ARABINOSIDE * * * n. a cytotoxic drug used to suppress the symptoms of some types of leukaemia. It is administered by injection and can damage the normal bone marrow, leading… … Medical dictionary
cytarabine — n. a drug that inhibits cell division (see antimetabolite) and is used to suppress the symptoms of acute myeloblastic leukaemia. It is administered by injection and can damage the normal bone marrow, leading to various blood cell disorders. Other … The new mediacal dictionary
cytarabine — An anticancer drug that belongs to the family of drugs called antimetabolites … English dictionary of cancer terms
cytarabine — /suy tar euh been /, n. Pharm. a toxic synthetic nucleoside, C9H13N3O5, used as an immunosuppressive and cytotoxic agent in the treatment of certain leukemias. Also cytosine arabinoside, ara C. [CYT(OSINE) + ARAB(INOSIDE) + INE2] … Useful english dictionary
cytarabine liposome injection — liposomal cytarabine … Medical dictionary
liposomal cytarabine — a suspension of cytarabine molecules encapsulated in liposomes; it is a sustained release preparation that is injected intrathecally in the treatment of meningitis associated with lymphoma … Medical dictionary
DepoFoam-encapsulated cytarabine — The anticancer drug cytarabine formulated inside small particles of a synthetic lipid material called DepoFoam. This dosage form slowly releases the drug and provides a sustained action … English dictionary of cancer terms