Cytosplat Mechanism of Action

Pharmacology: Pharmacodynamics: Cisplatin has biochemical properties similar to those of bifunctional alkylating agents. The drug inhibits DNA synthesis by producing intrastrand and interstrand cross links in DNA. Protein and RNA synthesis are also inhibited to a lesser extent.
Although the principal mechanism of action of cisplatin appears to be inhibition of DNA synthesis, other mechanisms, including enhancement of tumour immunogenicity, may be involved in its antineoplastic activity. Cisplatin also has immunosuppressive, radiosensitising, and antimicrobial properties.
Cisplatin does not appear to be cell cycle specific.
Pharmacokinetics: There is good uptake of cisplatin by the kidneys, liver and intestine. More than 90% of platinum containing species remaining in the blood are bound (possibly irreversibly) to plasma proteins.
Penetration into the CSF is poor although significant amounts of cisplatin can be detected in intracerebral tumours.
The clearance of total platinum from plasma is rapid during the first four hours after intravenous administration, but then proceeds more slowly because of covalent binding to serum proteins. Levels of unbound platinum fall with a half-life of 20 minutes to 1 hour depending on the rate of drug infusion.
The elimination of intact drug and various platinum-containing biotransformation products is via the urine. About 15-25% of administered platinum is rapidly excreted in the first 2-4 hours after administration of cisplatin. This early excretion is mostly of intact cisplatin. In the first 24 hours after administration, 20-80% is excreted, the remainder representing drug bound to tissues or plasma protein.