Oxaliplatin Chemical Properties

CAS DataBase Reference

63121-00-6(CAS DataBase Reference)

Oxaliplatin Usage And Synthesis

Pharmaceutical Applications

In 1930, the oxidised compound Oxophenarsine, containing an As＝O unit, was identified as the active ingredient and was later marketed under the trade name Mapharsen. Mapharsen was used until the 1940s when it was replaced by Penicillin. Mapharsen was actually synthesised in Ehrlich’s laboratory as compound number 5, but it was believed to be too toxic for any clinical application .
Generally, the use of arsenic-based drugs has ceased, especially as a result of the development of Penicillin. Nevertheless, Melarsoprol and an arsenic-based drug closely related to Atoxyl are licensed to treat sleeping sickness.

Pharmaceutical Applications

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 .

Pharmacokinetics

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.

Clinical Use

Antineoplastic platinum agent:
Treatment of metastatic colorectal cancer in combination with fluorouracil and folinic acid and stage III colon cancer

Side effects

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.

Enzyme inhibitor

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.

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: increased risk of nephrotoxicity and possibly ototoxicity with aminoglycosides, capreomycin, polymyxins or vancomycin.
Cytotoxics: avoid with panitumumab.
Antipsychotics: avoid with clozapine (increased risk of agranulocytosis).

Metabolism

Oxaliplatin is extensively metabolised by non-enzymatic biotransformation to both inactive and active compounds.
There is no in vitro evidence of cytochrome P450 metabolism of the diaminocyclohexane (DACH) ring.
Several cytotoxic biotransformation products including the monochloro-, dichloro- and diaquo-DACH platinum species have been identified in the systemic circulation together with a number of inactive conjugates.
Platinum removal is mainly by renal excretion and tissue distribution; platinum metabolites mainly by renal excretion. By day 5, approximately 54% of the total dose was recovered in the urine and <3% in the faeces.

Oxaliplatin(63121-00-6)Related Product Information

• Hexamethylenediamine
• 1,2-Cyclohexanedione
• 1,2-Diaminocyclohexane
• Oxaliplatin
• (+/-)-trans-1,2-Diaminocyclohexane
• Calcium oxalate
• Shikimic acid
• trans,trans-2,4-Undecadienal
• Oxaliplatin