Comparative pharmacokinetic study of idarubicin and daunorubicin in leukemia patients

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 (39.0 L/h/m2 for idarubicin versus 38.6 for daunorubicin), total volume of distribution (1756 versus 1725 L/m2) 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.