ドキソルビシン 化学特性,用途語,生産方法
解説
塩ドキソルビシン，赤橙色の針状晶．分解点204～205 ℃．[α]20D＋248°(メタノール)．UV(メタノール)λmax 233，252，288，479，496，529 nm．DNAに層間挿入して核酸合成を阻害する．トポイソメラーゼⅡを阻害してDNA鎖切断をする．急性リンパ性白血病，リンパ腫，乳がん，小細胞肺がん，卵巣がんなどの治療に広く使われる．
森北出版「化学辞典（第2版）
用途
ドキソルビシン（doxorubicin）は、抗悪性腫瘍剤（抗がん剤）の一種。
製造
ドキソルビシン，アドリアマイシンともいう．Streptomyces peucetius var caesiusが産生するアンスラサイクリン系抗生物質．
効能
抗悪性腫瘍薬, トポイソメラーゼII阻害薬
毒性
LD50 698 mg/kg(マウス，経口)．
化学的特性
Adriamycin is an orange to red cake-like or needle-like crystalline solid.
使用
Doxorubicin (adriamycin) is the most extensively studied of a family of highly fluorescent anthracycline antibiotics produced by several Streptomyces species, first reported in 1967 and later approved for human therapeutic use as an antitumour agent for the treatment of a wide range of cancers. Doxorubicin also exhibits anti-HIV and antibacterial activity. The mode of action of doxorubicin is thought to be due to intercalation of DNA and inhibition of nucleic acid synthesis.
適応症
Doxorubicin binds tightly to DNA by its ability to
intercalate between base pairs and therefore is preferentially
concentrated in nuclear structures. Intercalation
results in steric hindrance, hence production of
single-strand breaks in DNA and inhibition of DNA
synthesis and DNA-dependent RNA synthesis. The enzyme
topoisomerase II is thought to be involved in the
generation of DNA strand breaks by the anthracyclines.
Cells in S-phase are most sensitive to doxorubicin, although
cytotoxicity also occurs in other phases of the
cell cycle.
作用機序
Doxorubicin is not absorbed orally, and because of
its ability to cause tissue necrosis must not be injected
intramuscularly or subcutaneously. Distribution studies
indicate rapid uptake in all tissues except the CNS.
Extensive tissue binding, primarily intranuclear, accounts
for the prolonged elimination half-life.The drug
is extensively metabolized in the liver to hydroxylated
and conjugated metabolites and to aglycones that are
primarily excreted in the bile.
臨床応用
Doxorubicin is one of the most effective agents used
in the treatment of carcinomas of the breast, ovary, endometrium,
bladder, and thyroid and in oat cell cancer
of the lung. It is included in several combination regimens
for diffuse lymphomas and Hodgkin’s disease.
Doxorubicin can be used as an alternative to daunorubicin
in acute leukemias and is useful in Ewing’s sarcoma,
osteogenic sarcoma, soft-tissue sarcomas, and
neuroblastoma. Some activity has been reported in
non–oat cell lung cancer, multiple myeloma, and adenocarcinomas
of the stomach, prostate, and testis.
副作用
The most important toxicities caused by doxorubicin
involve the heart and bone marrow.Acutely, doxorubicin
may cause transient cardiac arrhythmias and
depression of myocardial function. Doxorubicin may
cause radiation recall reactions, with flare-ups of dermatitis,
stomatitis, or esophagitis that had been produced
previously by radiation therapy. Less severe toxicities
include phlebitis and sclerosis of veins used for
injection, hyperpigmentation of nail beds and skin
creases, and conjunctivitis. Because of its intense red
color, doxorubicin will impart a reddish color to the
urine for 1 or 2 days after administration.
安全性プロファイル
Confirmed carcinogen with experimental carcinogenic, neoplastigenic, and tumorigenic data. Poison by intraperitoneal, subcutaneous, parenteral, and intravenous routes. Human systemic effects by intravenous route: cardiac myopathy including infarction, nausea or vomiting, and effects on the hair. An experimental teratogen. Other experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits very toxic fumes of NO, and HCl
職業ばく露
An antibiotic product from streptomyces, used as anticancer drug
発がん性
Adriamycin is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
輸送方法
UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required.
不和合性
Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides
廃棄物の処理
It is inappropriate and possibly dangerous to the environment to dispose of expired or waste 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 properly label 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.
ドキソルビシン 上流と下流の製品情報
原材料
準備製品