Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK
Pharmacotherapeutic group: Anthracyclines and related substances
ATC code: L01DB06
Idarubicin is an antimitotic and cytotoxic agent which intercalates with DNA and interacts with topoisomerase II and has an inhibitory effect on nucleic acid synthesis.
The compound has a high lipophilicity which results in an increased rate of cellular uptake compared with doxorubicin and daunorubicin. Idarubicin has been shown to have a higher potency with respect to daunorubicin and to be an effective agent against murine leukaemia and lymphomas both by i.v. and oral routes. Studies in-vitro on human and murine anthracycline-resistant cells have shown a lower degree of cross-resistance for idarubicin compared with doxorubicin and daunorubicin. Cardiotoxicity studies in animals have indicated that idarubicin has a better therapeutic index than daunorubicin and doxorubicin. The main metabolite, idarubicinol, has shown in-vitro and in-vivo antitumoural activity in experimental models. In the rat, idarubicinol, administered at the same doses as the parent drug, is clearly less cardiotoxic than idarubicin.
After oral administration to patients with normal renal and hepatic function, idarubicin is rapidly absorbed, with a peak time of 2-4 hours., is eliminated from systemic circulation with a terminal plasma T½ ranging between 10-35 hours and is extensively metabolized to an active metabolite, idarubicinol, which is more slowly eliminated with a plasma T½ ranging between 33 and 60 hours. The drug is mostly eliminated by biliary excretion, mainly in the form of idarubicinol, urinary excretion accounting for 1-2% of the dose as unchanged drug and for up to 4.6% as idarubicinol.
Average values of absolute bioavailability have been shown to range between 18 and 39% (individual values observed in the studies ranging between 3 and 77%), whereas the average values calculated on the data from the active metabolite, idarubicinol, are somewhat higher (29-58%; extremes 12-153%).
Studies of cellular (nucleated blood and bone marrow cells) drug concentrations in leukaemic patients have shown that uptake is rapid and almost parallels the appearance of the drug in plasma. Idarubicin and idarubicinol concentrations in nucleated blood and bone marrow cells are more than two hundred times the plasma concentrations. Idarubicin and idarubicinol disappearance rates in plasma and cells were almost comparable.
No further preclinical safety data are available.
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