<p>Daunorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action. It forms complexes with DNA by intercalation between base pairs. It inhibits topoisomerase II activity by stabilizing the DNA- topoisomerase II complex, preventing the religation portion of the ligation- religation reaction that topoisomerase II catalyzes. Single strand and double-strand DNA breaks result. It may also inhibit polymerase activity, affect the regulation of gene expression, and produce free radical damage to DNA. It possesses an antitumor effect against a wide spectrum of animal tumors, either grafted or spontaneous.<br />
<br />
<strong>Distribution</strong>: Daunorubicin is rapidly and widely distributed in tissues, with the highest levels in the spleen, kidneys, liver, lungs and heart. The drug binds to many cellular components, particularly nucleic acids. There is no evidence that it crosses the blood-brain barrier, but the drug apparently crosses the placenta.<br />
<br />
<strong>Metabolism and Elimination</strong>: Daunorubicin is extensively metabolized in the liver and other tissues, mainly by cytoplasmic aldo-keto reductases, producing daunorubicinol, the major metabolite which has antineoplastic activity. Approximately 40% of the drug in the plasma is present as daunorubicinol within 30 minutes and 60% in 4 hours after a dose of Daunorubicin. Further metabolism via reduction cleavage of the glycosidic bond, 4-O demethylation, and conjugation with both sulfate and glucuronide have been demonstrated. Simple glycosidic cleavage of Daunorubicin or Daunorubicinol is not a significant metabolic pathway in man. Twenty-five percent of an administered dose of Daunorubicin is eliminated in an active form by urinary excretion and an estimated 40% by biliary excretion.</p>