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外観
白色～うすい黄色粉末～結晶
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用途
慢性リンパ球性白血病や多発性骨髄腫およぴリンパ種などの抗腫瘍薬として、また、関節リウマチや全身性エリテマトーデスおよび急性?慢性糸球体腎炎治療における免疫抑制剤などとして用いられる。
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効能
抗悪性腫瘍薬, アルキル化剤
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説明
Chlorambucil, approved by the Food and Drug Administration
(FDA) in 1957, is an antineoplastic/alkylating agent with
a broad spectrum of antitumor activity used to treat chronic
lymphocytic leukemia (CLL), Hodgkin’s and non-Hodgkin’s
lymphomas.
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化学的特性
Chlorambucil is a crystalline solid
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使用
Chlorambucil is a alkylating agent that is used as an chemotherapy drug in the treatment of chronic lymphocytic leukemia. Chlorambucil is also used to treat non-Hodgkin's lymphoma (NHL) and Hodgkin's
disease.
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定義
ChEBI: A monocarboxylic acid that is butanoic acid substituted at position 4 by a 4-[bis(2-chloroethyl)amino]phenyl group. A chemotherapy drug that can be used in combination with the antibody obinutuzumab for the treatment of chronic lymphocytic leukemia.
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適応症
Chlorambucil (Leukeran) is an aromatic nitrogen mustard
that is intermediate in chemical reactivity between
mechlorethamine and melphalan. Its mechanisms of action
and range of antitumor activity are similar to theirs.
It is well absorbed orally, but detailed information concerning
its metabolic fate in humans is lacking.
Chlorambucil is used primarily as daily palliative
therapy for chronic lymphocytic leukemia, Waldenstr?om’s
macroglobulinemia, myeloma, and other lymphomas.
Bone marrow toxicity is the major side effect of
chlorambucil. Nausea is uncommon or mild, and hair
loss does not occur. Chlorambucil shares the immunosuppressive,
teratogenic, and carcinogenic properties of
the nitrogen mustards.
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一般的な説明
Chlorambucil is available as 2-mg tablets for oral administrationin the treatment of Hodgkin’s lymphoma, andchronic lymphocytic leukemia in combination with prednisoneand as a single agent. The mechanisms of resistanceare the same as those seen for other agents of the class suchas mechlorethamine. The agent is well absorbed (75%) uponoral administration and highly protein bound. Metabolism ismediated by CYP and occurs extensively to give severalmetabolites, including the active phenylacetic acid–nitrogenmustard. The drug is eliminated via the kidneys with a terminalelimination half-life of 1.5 hours. Adverse effects includedose-limiting myelosuppression, which are seen asboth leucopenia and thrombocytopenia. Nausea and vomitingoccur less often than for mechlorethamine. Additionaladverse effects include hyperuricemia, azoospermia, amenorrhea,seizures, pulmonary fibrosis, and skin rash.
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空気と水の反応
Insoluble in water.
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反応プロフィール
Chloroambucil is an alkylating agent. Reacts with proteins and a variety of nucleophilic compounds .
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火災危険
Literature sources indicate that Chloroambucil is nonflammable.
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臨床応用
It is used in the palliative treatment of chronic lymphocytic leukemia,
malignant lymphoma, and Hodgkin's disease.
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安全性プロファイル
Confirmed carcinogen producing leukemia. Experimental
carcinogenic and neoplastigenic data. Poison
by ingestion, intravenous, intraperitoneal,
and subcutaneous routes. Human systemic
effects by ingestion: convulsions, cough,
dyspnea, and interstitial fibrosis. Human
reproductive effects by ingestion and
possibly other routes: changes in
spermatogenesis, menstrual cycle changes or
disorders, and teratogenic effects of the fetal
urogenital system. Experimental teratogenic
and reproductive effects. Human mutation
data reported. An anti-neoplastic agent.
When heated to decomposition it emits very
toxic fumes of Cland NOx.
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職業ばく露
Chlorambucil, an anticancer drug, is a
derivative of nitrogen mustard. This drug is primarily used
as an antineoplastic agent for treating lymphocytic leukemia; malignant lymphomas; follicular lymphoma; and
Hodgkin’s disease. The treatments are not curative but do
produce some marked remissions. Chlorambucil has also
been tested for treatment of chronic hepatitis, rheumatoid
arthritis; and as an insect chemosterilant. All of the chemical used in this country is imported from the United
Kingdom. Work exposure in the United States would be
limited to workers formulating the tablets, or to those
patients receiving the drug.
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発がん性
Chlorambucil is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans.
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環境運命予測
The mechanism of action of chlorambucil is thought to be an
alkylating agent and an aromatic nitrogen mustard derivative; it
interferes with DNA replication and RNA transcription by
alkylation and cross-linking the strands of DNA.
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輸送方法
UN2811 Toxic solids, organic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials, Technical
Name Required.
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純化方法
Chlorambucil is recrystallised from pet ether (flat needles) and has a solubility at 20o of 66% in EtOH, 40% in CHCl3, 50% in Me2CO but is insoluble in H2O [Everett et al. J Chem Soc 2386 1953]. [Beilstein 14 IV 1715.] CARCINOGEN.
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不和合性
Moisture. Chlorambucil is an alkylating
agent. Reacts with proteins and a variety of nucleophilic
compounds. Compounds of the carboxyl group react
with all bases, both inorganic and organic (i.e., amines)
releasing substantial heat, water, and a salt that may beharmful. Incompatible with arsenic compounds (releases
hydrogen cyanide gas), diazo compounds, dithiocarbamates, isocyanates, mercaptans, nitrides, sulfides (releasing
heat, toxic, and possibly flammable gases), thiosulfates,
and dithionites (releasing hydrogen sulfate and oxides of
sulfur).
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廃棄物の処理
It is inappropriate and possibly dangerous to the environment to dispose of expired or
waste drugs and pharmaceuticals by flushing them down
the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed
with wet cat litter or coffee grounds, double-bagged in
plastic, discard in trash. Larger quantities shall carefully
take into consideration applicable DEA, EPA, and FDA
regulations. If possible return the pharmaceutical to the
manufacturer for proper disposal being careful to properlylabel and securely package the material. Alternatively, the
waste pharmaceutical shall be labeled, securely packaged,
and transported by a state licensed medical waste contractor
to dispose by burial in a licensed hazardous or toxic waste
landfill or incinerator. Permanganate oxidation, high temperature incineration with scrubbing equipment, or microwave plasma treatment.
