daunomycin

Daunomycin, also known as daunorubicin, is an anthracycline antibiotic used as a chemotherapeutic agent. It is produced by Streptomyces species and is structurally related to doxorubicin. Daunomycin intercalates into DNA and inhibits topoisomerase II, thereby blocking DNA replication and transcription. It also generates free radicals that contribute to cytotoxicity.

In clinical use, daunomycin is employed primarily for hematologic malignancies. It is a standard component of combination regimens for acute myeloid leukemia (AML) and is used in some protocols for acute lymphoblastic leukemia (ALL), as well as in certain lymphomas and other solid tumors when combined with other agents. The conventional induction therapy for AML often includes daunorubicin with cytarabine. Daunomycin is administered intravenously; a liposomal formulation, DaunoXome, has been developed and is used for AIDS-related Kaposi’s sarcoma, among other indications.

Pharmacologically, daunomycin is metabolized in the liver and excreted mainly via the biliary system, with a multi-compartment pharmacokinetic profile that leads to significant tissue distribution, including the heart. This distribution underlies a major adverse effect: dose-dependent cardiotoxicity, which can lead to cardiomyopathy and heart failure. Other common adverse effects include myelosuppression, mucositis, nausea, vomiting, alopecia, and potential extravasation injury. Urine and other excretions may acquire a red or reddish-orange color.

Resistance to daunomycin can arise from reduced drug accumulation in cells, increased drug efflux, or alterations in topoisomerase II. Daunomycin is generally avoided or used with caution in pregnancy and must be monitored for cumulative cardiac toxicity during therapy.