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.
Robert
J
J
Fondation Bergonié, Bordeaux, France.
Rigal-Huguet
F
F
Hurteloup
P
P
D003630:Daunorubicin / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D015255:Idarubicin / Q000097:blood / Q000493:pharmacokinetics*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D015255:Idarubicin; D003630:Daunorubicin