The anthracycline glycoside antibiotics represent a group of potent anticancer 
agents with a wide spectrum of activity against solid tumours and haematological 
malignancies, and are the mainstay of a large number of clinical protocols for 
the treatment of adult and childhood neoplastic diseases. Their clinical 
activity is limited, however, by acute and chronic adverse effects. 
Myelosuppression, predominantly neutropenia and leucopenia, is the dose-limiting 
toxicity; in addition to this, mucositis, nausea, vomiting and alopecia are 
frequent, whereas hepatopathy, characterised by elevated bilirubin 
concentrations, occurs less frequently. Cardiotoxicity is a major adverse effect 
of the anthracycline antibiotics and can be acute or chronic; in the acute 
setting, electrocardiographic abnormalities may be seen, including ST-T 
elevations and arrhythmias, but chronic cardiotoxicity represents a serious 
adverse effect that may be lethal due to the development of irreversible, 
cumulative dose-dependent, congestive cardiomyopathy. The occurrence of toxicity 
displays a marked interindividual variation, and for this reason the 
pharmacokinetics and pharmacodynamics of anthracyclines have been extensively 
investigated in order to identify integrated models that can be used in the 
clinical setting to prevent the development of serious toxicity, mainly 
leucopenia, and maximise tumour exposure. Pharmacokinetics has been recognised 
to influence both the toxicity and the activity of anthracyclines; in 
particular, there is increasing evidence that the mode of administration plays 
an important role for cumulative cardiotoxicity and data indicate that bolus 
administration, rather than continuous infusion, appears to be an important risk 
factor for anthracycline-induced cardiomyopathy, thus implying that this type of 
toxicity is maximum concentration-dependent. On the contrary, exposure to the 
drug, as measured by area under the curve, seems best related to the occurrence 
of leucopenia. Finally, the development of pharmacokinetic-pharmacodynamic 
models allows the simulation of drug effects and ultimately dose optimisation in 
order to anticipate important toxicities and prevent their occurrence by the 
administration of prophylactic treatments.