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 Cytarabine hydrochloride

cytarabine is an antimetabolite analogue of cytidine with a modified sugar moiety (arabinose instead of ribose). Cytarabine is converted to the triphosphate form within the cell and then competes with cytidine for incorporation into DNA. Because the arabinose sugar sterically hinders the rotation of the molecule within DNA, DNA replication ceases, specifically during the S phase of the cell cycle. This agent also inhibits DNA polymerase, resulting in a decrease in DNA replication and repair. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Cytarabine was discovered in Europe in the 1960s. It was approved by the United States Food and Drug Administration in June 1969, and was initially marketed in the US by Upjohn under the trade name Cytosar-U. see http://en.wikipedia.org/wiki/Cytarabine.

DRUG DESCRIPTION

Cytarabine for Injection USP, commonly known as ara-C, an antineoplastic for intravenous, intrathecal, or subcutaneous administration, contains sterile lyophilized cytarabine (1-β-D-Arabinofuranosylcytosine). Cytarabine is an odorless, white to off-white, crystalline powder which is freely soluble in water and slightly soluble in alcohol and in chloroform. Cytarabine is a synthetic nucleoside which differs from the normal nucleosides cytidine and deoxycytidine in that the sugar moiety is arabinose rather than ribose or deoxyribose. Cytarabine for Injection USP is available in vials containing 100 mg, 500 mg, 1 g, and 2 g cytarabine. When necessary, the pH of Cytarabine for Injection USP was adjusted with hydrochloric acid and/or sodium hydroxide. Reconstitute with Bacteriostatic Water for Injection USP with benzyl alchohol for intravenous and subcutaneous use only. Do not use this diluent intrathecally. See "WARNINGS" Section.

Mechanism of Action

Cytosine arabinoside 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. When used as an antiviral, cytarabine functions by inhibiting deoxycytidine use. Cytarabine is rapidly deaminated in the body into the inactive uracil derivative and therefore is often given by continuous intravenous infusion. See http://en.wikipedia.org/wiki/Cytarabine.

Clinical uses

Cytarabine is mainly used in the treatment of acute myeloid leukaemia, acute lymphocytic leukaemia (ALL) and in lymphomas, 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, 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. 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. See http://en.wikipedia.org/wiki/Cytarabine.

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