Comparative pharmacokinetic study of idarubicin and daunorubicin in leukemia patients

Abstract We have studied the pharmacokinetics of idarubicin and daunorubicin in a total of 16 leukemic patients treated with one of these drugs associated with aracytine. The AUCs obtained for unchanged drugs were proportional to the dose, and the dose‐independent pharmacokinetic parameters were very similar for the two drugs: total plasma clearance (39·0L/h/m 2 for idarubicin versus 38·6 for daunorubicin), total volume of distribution (1756 versus 1725 L/m 2 ) and elimination half‐life (42·7 versus 47·4 h). The only metabolites detected were the 13–dihydroderivative of each drug, idarubicinol or daunorubicinol. The elimination half‐life of idarubicinol was two times higher than that of daunorubicinol (80·7 versus 37·3 h) which provided an AUC ratio metabolite/parent drug higher for idarubicin than for daunorubicin. In view of the fact that idarubicinol is a much more active metabolite than daunorubicinol, this protracted half‐life metabolite can account for the reported higher activity of idarubicin as compared to daunorubicin.