[Role of cell pharmacokinetics in the modulation of modalities in the administration of anthracyclines].

The rate of the anthracycline uptake and retention differs with the drug structure and with the cell type. Here we present evidence to show that as compared to carcinoma cells, normal epithelial cells are naturally resistant to adriamycin. Moreover, it is shown that uptake of demethoxy-daunorubicin and THP-ADM is a very rapid process as compared to ADM, epi-ADM or DNR. Cytotoxicity correlates with the intracellular concentration. The relevance of these in vitro findings is considered in the in vivo situation. Resistance to anthracyclines is in part related to decrease accumulation and retention. This resistance can be reversed not only by calcium transport and calmodulin inhibitors but also by co-treatment with aclacinomycin. Wether changes which occurred in acquired resistance can be found in cells with natural resistance to adriamycin remain to be determined.