Daunorubicin

Daunorubicin is an anthracycline that is sometimes referred to as an antitumor antibiotic. Daunorubicin inserts between base pairs of DNA to cause structural changes in DNA; however, the primary mechanism of cytotoxicity is the inhibition of topoi-somerase II. The pharmacokinetics are best described by a two-compartment model, with a terminal half-life of about 20 hours. The predominant route of elimination of daunorubicin and hydroxylated metabolites is hepatobiliary secretion. Daunorubi-cin has shown clinical activity in the treatment of acute lymphocytic leukemia, non-Hodgkin's lymphoma, neuroblastoma, and Ewing's and Kaposi's sarcomas. Myelosuppression is the major toxicity, along with alopecia, stomatitis, and mild to moderate nausea and vomiting, and it imparts a red to color to the urine so that patients need to be educated on side effects. Cardiac toxicity is dose related and manifested as congestive heart failure. To reduce the risk of cardiotoxicity, the maximum cumulative

dose in children older than 2 years of age is 300 mg/m , and the cumulative dose is 400 to 600 mg/m2 in adults. Ventricular ejection fractions should be measured before therapy, and periodically if therapy is continued. Therapy should be halted if there is a 10% to 20% decrease from baseline in ejection fraction. Daunorubicin is a vesicant also.

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