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Pharmacology: Pharmacodynamics: Carboplatin is a synthetic analogue of cisplatin. Like cisplatin, carboplatin interferes with DNA intrastrand and interstrand crosslinks in cells exposed to the drug. DNA reactivity has been correlated with cytotoxicity.
Pharmacokinetics: Following administration of carboplatin in man, linear relationships exist between dose and plasma concentrations of total and free ultrafilterable platinum.
Repeated dosing during 4 consecutive days did not produce an accumulation of platinum in plasma.
Following administration of carboplatin, reported values for the terminal elimination half-lives of free ultrafilterable platinum and carboplatin in man were approximately 6 hours and 1.5 hours, respectively. During the initial phase, most of the free ultrafilterable platinum is present as carboplatin. The terminal half-life for total plasma platinum is 24 hours. Approximately 87% of the plasma platinum is protein-bound within 24 hours following administration.
Carboplatin is excreted primarily in the urine with recovery of approximately 70% of the administered platinum within 24 hours. Most of the drug is excreted in the first 6 hours. Excretion of carboplatin is by glomerular filtration.
Patients with poor renal function have a higher area under curve (AUC) for total platinum, and a reduction in dosage is recommended.
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