PHARMACOKINETICS OF DOXORUBICIN AND ITS ACTIVE METABOLITE IN PATIENTSWITH NORMAL RENAL-FUNCTION AND IN PATIENTS ON HEMODIALYSIS

The comparative pharmacokinetics of doxorubicin (DOX) were investigate d in five hemodialysis (HD) and eight non-hemodialysis (non-HD) patien ts who were infused with a 40- to 60-mg dose of DOX at a constant rate over 30 min. A significant difference was observed in the total body clearance (Cl tot) of DOX between HD and non-HD patients. The area und er the curve (AUC) for both DOX and doxorubicinol (DOXol), an active m etabolite, showed increases of approximately 1.5 and 3 times in HD pat ients as compared with non-HD patients. Although these differences wer e not statistically significant (P <0.1), the mean residence time (MRT ) of DOX and DOXol in HD patients showed a 2-fold increase in comparis on with those in non-HD patients. Compartmental analysis indicated tha t the greater AUC values and longer MRT of DOX and DOXol in HD patient s resulted from the lesser DOXol formation and disappearance of rate c onstants. As a consequence of the decrease in Cl tot for DOX and the m arginal hemodialysis clearance of both DOX and DOXol, the present stud y suggests that the exposure to DOX and DOXol obtained in HD patients greater that achieved in non-ID patients. Careful attention should the refore be paid to HD patients receiving DOX.