Pharmacotherapeutic Group: Other antineoplastic agents, Platinum compounds. ATC Code: L01XA01.
Pharmacology: Pharmacodynamics: Cisplatin is an inorganic compound which contains a heavy metal [cis-diamminedichloridoplatinum (II)]. It inhibits DNA-synthesis by the formation of DNA cross-links. Protein and RNA synthesis are inhibited to a lesser extent.
Although the most important mechanism of action seems to be inhibition of DNA synthesis, other mechanisms can also contribute to the antineoplastic activity of cisplatin, including the increase of tumour immunogenicity. The oncolytic properties of cisplatin are comparable to the alkylating agents. Cisplatin also has immunosuppressive, radio sensitising, and antibacterial properties. Cisplatin seems to be cell-cycle non-specific. The cytotoxic action of cisplatin is caused by binding to all DNA-bases, with a preference for the N-7 position of guanine and adenosine.
Pharmacokinetics: After intravenous administration cisplatin quickly distributes across all tissues; cisplatin badly penetrates in the central nervous system. The highest concentrations are reached in the liver, kidneys, bladder, muscle tissue, skin, testes, prostate, pancreas and spleen.
After intravenous administration the elimination of filterable, non-protein bound cisplatin runs biphasic, with an initial and terminal half-life of 10-20 minutes and 32-53 minutes, respectively.
The elimination of the total quantity of platinum runs triphasic with half-lives of 14 minutes, and 274 minute and 53 days respectively.
Cisplatin is bound to plasma proteins for 90%.
The excretion primarily takes place via the urine: 27-43% of the administered dose is recovered in the urine in the first five days after the treatment. Platinum is also excreted in the bile.