Cytarabine

Cytarabine

Cytarabine
Systematic (IUPAC) name
4-amino-1-[(2R,3S,4R,5R)-3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl] pyrimidin-2-one
Clinical data
Trade names Cytosar-U
AHFS/Drugs.com
MedlinePlus
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
Legal status
  • (Prescription only)
Routes of
administration
Injectable (intravenous injection or infusion, intrathecal, or subcutaneously)
Pharmacokinetic data
Bioavailability 20% oral
Protein binding 13%
Metabolism Liver
Biological half-life biphasic: 10 min, 1-3 hr
Excretion Renal
Identifiers
CAS Registry Number  Y
ATC code L01
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  Y
ChEMBL  Y
Chemical data
Formula C9H13N3O5
Molecular mass 243.217 g/mol
 Y   

Cytarabine or cytosine arabinoside (Cytosar-U or Depocyt) 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.[1] It is also known as ara-C (arabinofuranosyl cytidine).[2] It kills cancer cells by interfering with DNA synthesis.

It is called cytosine arabinoside because it combines a health system.[4]

Contents

  • Medical uses 1
  • Side effects 2
  • Mechanism of action 3
  • History 4
  • Brand names 5
  • References 6
  • External links 7

Medical uses

Cytarabine is mainly used in the treatment of acute myeloid leukaemia, acute lymphocytic leukaemia (ALL) and in lymphomas,[5] 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[6] 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.

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.[7]

To prevent the side effects and improve the therapeutic efficiency, various derivatives of this drugs (including amino acid, peptide, fatty acid and phosphates) have been evaluated, as well as different delivery systems.[8]

Mechanism of action

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[9] and RNA polymerases and nucleotide reductase enzymes needed for DNA synthesis.

When used as an antiviral, cytarabine functions by inhibiting deoxycytidine use.[10]

Cytarabine is rapidly deaminated in the body into the inactive uracil derivative and therefore is often given by continuous intravenous infusion.

History

Cytarabine was first synthesized in 1959 by Richard Walwick, Walden Roberts, and Charles Dekker at the University of California, Berkeley.[11]

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.

Brand names

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

References

  1. ^ Wang WS, Tzeng CH, Chiou TJ; et al. (June 1997). "High-dose cytarabine and mitoxantrone as salvage therapy for refractory non-Hodgkin's lymphoma". Jpn. J. Clin. Oncol. 27 (3): 154–7.  
  2. ^ 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.  
  3. ^ Feist, Patty (April 2005). "A Tale from the Sea to Ara C". 
  4. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  5. ^ 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.  
  6. ^ 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.  
  7. ^ 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.  
  8. ^ Chhikara BS, Parang K (2010). "Development of cytarabine prodrugs and delivery systems for leukemia treatment". Expert Opinion on Drug Delivery 7 (12): 1399–1414.  
  9. ^ Perry, Michael J. (2008). The Chemotherapy source book. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 80.  
  10. ^ Lemke, Thomas L.; Williams, David H.; Foye, William O. (2002). Foye's principles of medicinal chemistry. Hagerstwon, MD: Lippincott Williams & Wilkins. p. 963.  
  11. ^ Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. p. 258.  

External links

  • 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.