Daunorubicin

Daunorubicin is an anthracycline glycoside antibiotic and is a potent antileukaemia agent. It also has immunosuppressant effects.

The exact mechanism of the antineoplastic action of daunorubicin is uncertain but may involve binding to DNA and RNA by intercalation between base pairs and inhibition of DNA and RNA synthesis by template disordering and steric obstruction. Daunorubicin is most active in the S phase of cell division but is not cycle phase-specific. Tumour cell cross-resistance has been observed between daunorubicin and doxorubicin.

No controlled paediatric studies have been conducted.

The literature mentions the use of daunorubicin in treatment regimens for Acute Myelogenous Leukaemia and Acute Lymphocytic Leukaemia, including paediatric age groups. However, due to the ongoing search for a balance in gain or maintenance of efficacy and a decrease in toxicity the use of daunorubicin in the treatment of paediatric ALL and AML is fluctuating in clinical practice, mainly depending on risk stratification and specific subgroups. Published studies suggest no differences in safety profile between paediatric patients and adults.

Daunorubicin is rapidly taken up by the tissues, especially by the kidneys, spleen liver and heart. It does not cross the blood brain barrier. Subsequent release of the drug and its metabolites from the tissues is slow (T_½ = 55 hours). Daunorubicin is rapidly metabolised in the liver. The major metabolite, daunorubicinol is also active. Daunorubicin is excreted slowly in the urine, mainly as metabolites with 25% excreted in the first 5 days. Biliary excretion also makes a significant (40%) contribution to elimination.

Daunorubicin is genotoxic and carcinogenic in rats and mice. Daunorubicin has been shown to induce chromosomal damage in the in vitro chromosomal aberration test on human lymphocytes, and in vivo on human lymphocytes and on human and rat bone marrow cells. Daunorubicin induced mutagenicity in the bacterial reverse mutation (Ames) test.

Daunorubicin showed teratogenic and embryotoxic effects in animal studies. Furthermore, daunorubicin caused testicular atrophy and total aplasia of spermatocytes in the seminiferous tubules in dogs.