PHARMACOKINETICS AND TISSUE DISTRIBUTION OF IDARUBICIN AND ITS ACTIVEMETABOLITE IDARUBICINOL IN THE RABBIT

A three-compartment model was fitted to idarubicin data in a NONMEM po oled-data approach. Clearance (CL) of 221.7 ml/min was relatively high , and drug distribution was rapid (CL(D)=248.3 ml/min) and extensive [ steady-state volume of distribution (V-ss) 24 1]. The area under the c oncentration-time curve (AUG) of idarubicinol was 8 times that of idar ubicin. Concentrations of idarubicin (idarubicinol) measured in the my ocardium at 24 h after i.v. administration of idarubicin were 20 (5) t imes those determined in plasma. Tissue concentrations of idarubicinol were up to 400 times those of idarubicin, indicating that the active metabolite contributes significantly to the overall drug action.