Oxaliplatin 化学特性,用途語,生産方法
用途
白金製剤に分類される抗癌剤
特徴
体内で活性体に変換され、その活性体が癌細胞内のDNAとも結合する。この結合のためDNAの複製および転写が阻害される。
シスプラチンに比べて副作用の少なさなどの面で優れている。
応用例（製薬）
Oxaliplatin (cis-[oxalato] trans-1,2-diaminocyclohexane platinum(II)), for example, marketed under the
trade name Eloxatin, is considered as a third-generation platinum-based anticancer drug. Its structure
differs from previously synthesised platinum compounds by the configuration of its amino substituents. Its
platinum centre is coordinated by two chelating ligands, namely an oxalate ligand and a so-called DACH
(1,2-diaminocyclohexane) ligand. In comparison to cisplatin, the two chlorine leaving groups are replaced
by an oxalato leaving group. The simple amino groups are replaced by the DACH ligand, which is the
nonleaving group.
The clinical use of oxaliplatin was approved by the European Union in 1999 and by the FDA in 2002. It
is most effective in combination with 5-fluorouracil and leucovorin (5-FU/LV) in the treatment of metastatic
carcinomas of the colon or rectum. Oxaliplatin induces less side effects than cisplatin; for example, it is
less nephrotoxic and ototoxic and leads to less myelosuppression. Unfortunately, treatment with oxaliplatin
can lead to nerve damage, which may not be reversible in the case of chronic exposure of the patient to the
drug. Oxaliplatin is usually administered intravenously as infusion over a period of 2–6 h in doses similar to
cisplatin. The neurotoxic side effects are dose-limiting .
薬物動態学
Oxaliplatin decomposes in alkaline media and should not be coadministered with drugs that will increase the pH of the IV solution. Oxaliplatin is used in the treatment of metastatic colon or rectal cancer, either alone or in combination with 5-fluorouracil.
副作用
Oxaliplatin often retains activity in patients who are no longer responding to the “first-generation” organometallics and also is significantly less mutagenic, nephrotoxic, hematotoxic, and ototoxic than cisplatin.
酵素阻害剤
This potent anti-cancer drug (FW = 397.29 g/mol; CAS 63121-00-6; IUPAC Name: [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato- O,O')platinum(II)), also known as Eloxatin?, is a intravenously administered DNA crosslinker and mutagen. The combination of amine group- and carboxyl group-donating bidentate ligands results in significantly lower pharmacologic inactivation as a consequence of nonenzymatic hydrolysis. (See also Cisplatin (for mechanism of action) and Carbonatoplatin) Unlike cisplatin, oxaliplatin forms both interstrand and intrastrand DNA cross links that prevent DNA replication and transcription, thereby promoting programmed cell death. Oxaliplatin also crosses the blood-brain barrier. Key Pharmacokinetic Parameters: See Appendix II in Goodman & Gilman’s THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, 12th Edition (Brunton, Chabner & Knollmann, eds.) McGraw-Hill Medical, New York.
Oxaliplatin 上流と下流の製品情報
原材料
準備製品