シタラビン 化学特性,用途語,生産方法
外観
白色～ほとんど白色粉末～結晶
用途
シトシン系代謝拮抗物質です。
DNA ポリメラーゼⅠ阻害作用を示します。
効能
抗悪性腫瘍薬, 代謝拮抗薬, 抗ウイルス薬, DNAポリメラーゼ阻害薬
商品名
キロサイド (日本新薬); キロサイド (日本新薬)
化学的特性
A white or almost white, crystalline powder, freely soluble in water, very slightly soluble in alcohol and in methylene chloride.
使用
Cytarabine USP (Cytosar)is used to treat Acute granulocytic leukemia (adults); acute lymphocytic leukemia (children); Hodgkin’s disease
適応症
Cytarabine (cytosine arabinoside, ara-C, Cytosar-U) is
an analogue of the pyrimidine nucleosides cytidine and
deoxycytidine. It is one of the most active agents available
for the treatment of acute myelogenous leukemia.
Cytarabine kills cells in the S-phase of the cycle by competitively
inhibiting DNA polymerase. The drug must
first be activated by pyrimidine nucleoside kinases to
the triphosphate nucleotide ara-cytosine triphosphate
(ara-CTP). The susceptibility of tumor cells to cytarabine
is thought to be a reflection of their ability to activate
the drug more rapidly (by kinases) than to inactivate
it (by deaminases).
定義
ChEBI: A pyrimidine nucleoside in which cytosine is attached to D-arabinofuranose via a beta-N1-glycosidic bond.
一般的な説明
Cytarabine is a pyrimidine nucleoside drug that is related toidoxuridine. This agent is primarily used as an anticanceragent for Burkitt lymphoma and myeloid and lymphaticleukemias. Cytarabine blocks the cellular utilization of deoxycytidine,hence inhibiting the replication of viral DNA.Before it becomes active, the drug is converted to monophosphates,diphosphates, and triphosphates, which block DNApolymerase and the C-2 reductase that converts cytidinediphosphate into the deoxy derivative.
The antiviral use of cytarabine is in the treatment of herpeszoster (shingles), herpetic keratitis, and viral infectionsthat resist idoxuridine. Cytarabine is usually administeredtopically. Toxicity occurs on bone marrow, the gastrointestinal(GI) tract, and the kidneys.
空気と水の反応
Water soluble.
健康ハザード
ACUTE/CHRONIC HAZARDS: Very toxic. Hazardous decomposition products. May cause irritation on contact. Teratogen. Mutagen. Central nervous system effects.
作用機序
Cytarabine is rapidly metabolized in the liver, kidney,
intestinal mucosa, and red blood cells and has a
half-life in plasma of only 10 minutes after intravenous
bolus injection. The major metabolite, uracil arabinoside
(ara-U), can be detected in the blood shortly after
cytarabine administration. About 80% of a given
dose is excreted in the urine within 24 hours, with less
than 10% appearing as cytarabine; the remainder is
ara-U.When the drug is given by continuous infusion,
cytarabine levels in CSF approach 40% of those in
plasma.
臨床応用
Cytarabine is used in the chemotherapy of acute
myelogenous leukemia, usually in combination with an
anthracycline agent, thioguanine, or both. It is less useful
in acute lymphoblastic leukemia and the lymphomas
and has no known activity against other tumors. It has
been used intrathecally in the treatment of meningeal
leukemias and lymphomas as an alternative to methotrexate.
安全性プロファイル
Moderate to low toxicity byingestion. Human systemic effects: allergic dermatitis,ataxia, blood changes, central nervous system effectsconjunctive irritation, degenerative brain changes, hearingacuity change, lachrymation, peripheral nervefasciculati
純化方法
Purify cytarabin by recrystallisation from aqueous EtOH or a large volume of H2O (it solubility at ~20o is 5%). It has max 212 and 279nm at pH 2 and 272nm at pH 12. It is an acute leukaemic agent. [Walwick et al. Proc Chem Soc (London) 84 1959, Beilstein 25 III/IV 3669.]
シタラビン 上流と下流の製品情報
原材料
準備製品