Pharmacotherapeutic Group: Antineoplastic agent.
Pharmacology: Pharmacodynamics: Mechanism of Action: Cisplatin is a platinum compound of which only the cis-isomer is active. It appears to produce intraand interstrand cross links which modify DNA structure and inhibit DNA synthesis. In addition, and to a lesser extent, cisplatin inhibits protein and RNA synthesis. It does not appear to be phase-specific in the cell cycle.
Pharmacokinetics: Distribution: Cisplatin seems to concentrate in the liver, kidneys, small intestine and testes. It does not cross the blood brain barrier so does not penetrate the cerebrospinal fluid (CSF) to any great extent. CSF levels of cisplatin are low although significant amounts can be detected in intracerebral tumours. Animal studies show good uptake into ovarian and uterine tissue.
Elimination and Excretion: After IV injection, plasma decay is biphasic. The initial phase is rapid with a half-life of 25-49 minutes and this is followed by a prolonged elimination phase with a half-life of 2-4 days. This long elimination phase is probably due to a high degree of protein binding. Normally more than 90% is bound to plasma proteins, but this may be more during a slow infusion. Excretion is predominantly renal. About 15-25% of a dose is rapidly excreted, mainly as intact drug, in the first 2-4 hours and 20-75% in the first 24 hours. The remainder represents drug bound to tissues or plasma proteins.