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There is a linear correlation with co-morbidity, number of pills and organ dysfunctions. Organ dysfunction as well as a multiplicity of co-drugs have to be a matter of concern in using full dosages. It is a matter of experience and an expert decision to treat patients with full dosages. Insights into the interaction of anthracyclines and other drugs are rare. No systematic pharmacokinetic studies have been performed. Verapamil has an influence on PK parameters of EPI as well on the metabolism. The AUC of EPI is lower under the influence of verapamil whereas the metabolism of the glucuronides are enhanced .
24 K. Mross et al. Drug–cell membrane interactions Each drug which is administered iv or po is present with a certain concentration in the central compartment where the amount can be determined (see section pharmacokinetics). To enter the tumor cell, the anthracycline must leave the blood vessels, enter the interstitial tissue und penetrate and cross the cell membrane in order to reach the inner compartment of the cell. The transmembrane movement of the anthracyclines occurs by free diffusion of the non-ionized drug .
The cumulative doses are 550 mg/m2 for DOX, 800 mg/m2 for DNR and 900 mg/m2 for EPI [33, 85–88]. For IDA no such data are available. The 5% risk for CHF was estimated within the range 120–240 mg/m2. The above mentioned data were published in the 1970s and 1980s. Figure 6 shows the incidence of CHF related to cumulative anthracycline doses. The lin-log plot shows in principal similar curves for DOX and EPI but EPI’s curve is shifted parallel to higher dose levels which reflects the higher dose necessary to damage the heart to the same degree than after DOX.