ミトキサントロン二塩酸塩 化学特性,用途語,生産方法
外観
暗い緑色～濃い紫色～黒色粉末～結晶
用途
医薬(抗悪性腫瘍剤) (NITE CHRIP)
用途
アントラサイクリン系抗生物
質です。DNA 鎖と架橋を形成し、核酸合成を
阻害します。また、トポイソメラーゼⅡを阻
害し、DNA 合成を阻害します。
効能
抗悪性腫瘍薬, トポイソメラーゼII阻害薬
商品名
ノバントロン (あすか製薬)
使用上の注意
不活性ガス封入
説明
Mitoxantrone hydrochloride is the first of the synthetic anthracenediones related
to doxorubicin to reach the marketplace. Mitoxantrone is useful in the treatment
of advanced localized and metastatic mammary carcinomas. It is reported to be
less cardiotoxic than doxorubicin.
化学的特性
Dark blue, electrostatic, hygroscopic powder.
使用
analgesic, antipyretic
一般的な説明
Mitoxantrone is supplied as a blue aqueous solution in 10-and 20-mg vials for IV administration in the treatment of acute lymphoid leukemia, acute myeloid leukemia, breastcancer, prostate cancer, non-Hodgkin’s lymphoma, andmultiple sclerosis. The mechanisms of resistance are thesame as those seen for the anthracyclines. The distributionhalf-life is 1.1 to 3.1 hours, and the drug has a large volumeof distribution (11 L/kg). The elimination half-life rangedfrom 23 to 215 hours, and elimination was primarily via thebile. Metabolism of the agent involves oxidation of the sidechainalcohols to give the monocarboxylic and dicarboxylicacids.Other toxicities are those seen for the anthracyclinesand include myelosuppression, nausea, vomiting, mucositis,diarrhea, and alopecia. The intense color of the parent drugand metabolites may turn the urine blue.
生物活性
Mitoxantrone hydrochloride (Mitoxantrone dihydrochloride) is a type II DNA topoisomerase inhibitor. Disrupts DNA synthesis and repair and induces damage by DNA cross-linking. Also inhibits PIM1 kinase (IC50 = 51 nM). Immunomodulatory, antineoplastic and chemotherapeutic agent. Also USP11 inhibitor (IC50= 3.15 μM). Induces cell death of pancreatic cancer cell lines expressing wild-type BRCA2.
臨床応用
Mitoxantrone is used in combination with other agents during the initial treatment of acute nonlymphocytic leukemia and hormone-refractory prostate cancer. Recent studies have shown that mitoxantrone also decreases the rate of relapse and disease progression in patients with multiple sclerosis. Although too toxic for use in patients with primary progressive disease, it is available for the treatment of chronic progressive, progressive relapsing, or deteriorating relapsing-remitting multiple sclerosis.
代謝
Mitoxantrone excretion primarily is biliary. Both the unchanged drug and inactive metabolites resulting from N-dealkylation, deamination, and oxidation of the resultant aldehyde to the carboxylic acid are observed. Both arms of the structure can be metabolized, leading to mono- or dicarboxylic acid metabolites, which are excreted as the glucuronide conjugate. The conjugated metabolites are an intense, dark blue in color and will result in blue-green urine.
ミトキサントロン二塩酸塩 上流と下流の製品情報
原材料
準備製品