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  • Title: Clinical pharmacokinetics of epirubicin.
    Author: Robert J.
    Journal: Clin Pharmacokinet; 1994 Jun; 26(6):428-38. PubMed ID: 8070217.
    Abstract:
    Epirubicin (4'-epidoxorubicin) is a new anthracycline that has activity similar to doxorubicin (adriamycin) in a variety of solid neoplasms and haematologic malignancies. Importantly, epirubicin causes less cardiotoxicity than doxorubicin. There is extensive distribution of epirubicin into tissues and the elimination of the drug is predominantly biliary, with less than 15% of the drug excreted in the urine. The metabolism of epirubicin is characterised by complex biotransformation to relatively or totally inactive metabolites, including a 13-dihydro derivative, epirubicinol, 2 glucuronides and 4 aglycones. Quantitatively, the glucuronides of epirubicin and epirubicinol are very important, and this pathway, which is unique to epirubicin metabolism in humans, might explain the better tolerability of this drug compared with doxorubicin. Epirubicin pharmacokinetics may be described by a 3-compartment model, with median half-life values of 3.2 minutes, 1.2 and 32 hours for each phase. Total plasma clearance is 46 L/h/m2 and volume of distribution at steady-state is 1000 L/m2. The pharmacokinetics of epirubicin appears to be linear for doses up to the maximal tolerated dose of 150 to 180 mg/m2. Both intraperitoneal and intravesical administration of epirubicin are feasible, but remain of a rather restricted interest. The area under the plasma concentration-time curve of epirubicin is fairly well correlated with the relative kill of white blood cells. Therefore, epirubicin clearance can be used to predict haematological toxicity.
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