Source: Health Products Regulatory Authority (ZA) Revision Year: 2021 Publisher: Pfizer Laboratories (Pty) Ltd, 85 Bute Lane, Sandton 2196, South Africa Tel: +27 (0)11) 320 6000 / 0860 734 937 (Toll-free South Africa)
Category and class: A26 Cytostatic agents
Daunorubicin is an antineoplastic antibiotic which is structurally related to doxorubicin. The medicine appears to act by inhibiting DNA and DNA-dependent RNA synthesis by forming a complex with DNA with intercalation between base pairs and uncoiling of the helix. Daunorubicin may also inhibit polymerase activity, affect regulation of gene expression, and be involved in free radical damage to DNA.
Daunorubicinis not cell cycle-phase specific although maximum cytotoxic activity occurs in the S phase.
Daunorubicin also has antibacterial and immunosuppressive properties.
Daunorubicin is rapidly and widely distributed in tissues, with highest levels in the heart, kidneys, liver, lungs and spleen. It binds inside the cells to cellular components, mainly nucleic acids.
Daunorubicin does not cross the blood-brain barrier but appears to cross the placenta. It is not known if daunorubicin is present in breast milk.
Daunorubicin is extensively metabolised 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 medicine in the plasma is present as daunorubicinol within 30 minutes and 60% in 4 hours after a dose of daunorubicin. Additional metabolism by reductive cleavage of the glycosidic bond produces aglycones, which have little or no cytotoxic activity and are demethylated and conjugated with sulphate and glucuronide by microsomal enzymes.
Daunorubicin metabolism may be altered in patients with impaired hepatic function.
Following rapid IV administration, total plasma concentrations of daunorubicin and its metabolites decline in a triphasic manner and plasma concentrations of unchanged daunorubicin decline in a biphasic manner.
The plasma half-life of daunorubicin averages 45 minutes in the initial phase and 18,5 hours in the terminal phase. By 1 hour after administration of daunorubicin, the predominant form of daunorubicin in plasma is the metabolite daunorubicinol, which has an average terminal plasma half-life of 26,7 hours.
Daunorubicin and its metabolites are excreted in the urine and bile, with urinary excretion accounting for 14-23% of the dose. Most urinary excretion of daunorubicin occurs within 3 days. After the first 24 hours, daunorubicinis excreted in urine mainly as daunorubicinol. An estimated 40% of a dose is eliminated by biliary excretion.
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