Naproplat Mechanism of Action

Antineoplastic.
Pharmacology: Mechanism of Action: Carboplatin is second-generation platinum compound that may be classified as a non-classical alkylating agent and is cell-cycle nonspecific. It is a cytotoxic platinum complex that reacts with nucleophilic sites of DNA. This causes intrastrand and interstrand cross links and DNA protein cross links, which inhibit DNA, RNA and protein synthesis.
Pharmacokinetics: Following administration of Carboplatin, the majority of the dose is rapidly cleared from the blood and largely excreted in urine within 6 hours. The remaining drug is eliminated in a biphasic manner, with mean half-life of 2.5 hours and about 5 days. The rate of binding of plasma protein is significantly lower accounting for the proportion of free drug available for rapid excretion. The degree of urinary excretion indicates less organ retention of the drug. The major route of elimination of carboplatin is renal excretion. Patients with creatinine clearance of approximately 60 mL/min or greater excrete 65% of the dose in the urine within 12 hours and 71% of the dose within 24 hours. All the platinum in the 24-hour urine is present as Carboplatin. Only 3% to 5% of the administered platinum is excreted in the urine between 24 and 96 hours. In patients with creatinine clearance below 60 mL/min, the total body and renal clearances of Carboplatin decrease as the creatinine clearance decreases and therefore reduced renal function increases the serum half-life of Carboplatin and results in increased myelotoxicity. Carboplatin dosages should, therefore, be reduced in these patients since carboplatin is eliminated almost completely by glomerular filtration, there is little concentration of carboplatin at the renal tubular level which may account for its diminished nephrotoxic potential as compared to cisplatin.