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効能
抗悪性腫瘍薬, アルキル化剤
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化学的特性
White Solid
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使用
An antitumor agent which also acts as a chemosterilant for male houseflies and other insects. Antineoplastic.
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定義
A hexamethyl-2,4,6-
triamine derivative of 1,3,5-triazine.
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適応症
Although both DNA and RNA synthesis are inhibited
in cells exposed to hexamethylmelamine (Hexalen), the
molecular mechanisms of these effects are not known.
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一般的な説明
Altretamine is available in 50-mg capsules for oraladministration as a second-line treatment for ovarian cancer.The mechanism of action has not been firmly established, althoughthe spectrum of activity is similar to that for otheralkylating agents; however, cross-resistance is not seen.Cytotoxicity has been correlated with metabolism to give thecarbinolamines, which may form imines capable of crosslinking,or decompose to give formaldehyde, which may reactwith nucleophiles on DNA or proteins. The agent is well absorbedupon oral administration, well distributed, and highly(90%) plasma protein bound. The agent is extensively metabolizedin the liver by CYP to give demethylated metabolites via the previously mentioned carbinolamines. Elimination occursprimarily in the urine as mostly demethylated metaboliteswith a terminal elimination half-life of 4 to 10 hours.Myleosuppression and nausea/vomiting are dose-limitingtoxicities. Other adverse effects include lethargy, agitation,hallucinations, skin rash, and elevations in transaminase levels,flulike symptoms, abdominal cramps, and diarrhea.
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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
Altretamine neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides.
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危険性
Toxic.
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作用機序
Hexamethylmelamine is readily absorbed after oral
administration, with peak plasma levels achieved after 1
hour.The drug is readily metabolized to form a number
of demethylated metabolites. Urinary elimination is the
primary route of drug excretion.
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臨床応用
Hexamethylmelamine is useful for the treatment of
ovarian adenocarcinoma and is frequently combined
with cyclophosphamide, cisplatin, and doxorubicin in
the treatment of this tumor. It also has some activity
against small cell lung cancer.
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副作用
Nausea and vomiting are the major toxicities associated
with hexamethylmelamine administration. Myelosuppression
and a peripheral neuropathy also may
occur.
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代謝
This unique structure is believed to damage tumor cells through the production of the weakly alkylating species formaldehyde, a product of CYP450-mediated N-demethylation. Administered orally, altretamine is extensively metabolized on first pass, producing primarily mono- and didemethylated metabolites. Additional demethylation reactions occur in tumor cells, releasing formaldehyde in situ before the drug is excreted in the urine.
