Pharmacokinetics and metabolism

After IV administration, anthracycline levels fall rapidly as it is distributed and binds to tissue DNA. Subsequent metabolism and elimination leads to a slow fall in plasma concentrations over several days.

The principal route of metabolism is by reduction and subsequent hepatic elimination. The significance of liver dysfunction in altering anthracycline kinetics has been controversial. Dose reductions are, however, recommended for patients with abnormal liver biochemistry tests as they are at risk of increased toxicity. Dose reductions are not usually required for patients with impaired renal function.

Structural differences affect the pharmacology and clinical use of anthracycline analogues. Epirubicin differs from doxorubicin only by the orientation of a single -OH group, but this enables glucuronida-tion in the liver and more rapid elimination.

Idarubicin has a different side-chain from daunorubicin making it more lipid-soluble and allowing oral in addition to IV administration. It is also distinctive in that the metabolite idarubicinol retains greater cytotoxic activity than metabolites of other anthracyclines.

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