Pharmacokinetics of doxorubicin and its active metabolite in patients with normal renal function and in patients on hemodialysis.
The comparative pharmacokinetics of doxorubicin (DOX) were investigated in five hemodialysis (HD) and eight non-hemodialysis (non-HD) patients 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 under the curve (AUC) for both DOX and doxorubicinol (DOXol), an active metabolite, showed increases of approximately 1.5 and 3 times in HD patients as compared with non-HD patients. Although these differences were not statistically significant (P < 0.1), the mean residence time (MRT) of DOX and DOXol in HD patients showed a 2-fold increase in comparison with those in non-HD patients. Compartmental analysis indicated that the greater AUC values and longer MRT of DOX and DOXol in HD patients resulted from the lesser DOXol formation and disappearance of rate constants. As a consequence of the decrease in Cl tot for DOX and the marginal hemodialysis clearance of both DOX and DOXol, the present study suggests that the exposure to DOX and DOXol obtained in HD patients greater than achieved in non-HD patients. Careful attention should therefore be paid to HD patients receiving DOX.
Yoshida
H
H
Department of Hospital Pharmacy, Nagoya Memorial Hospital, Japan.
Goto
M
M
Honda
A
A
Nabeshima
T
T
Kumazawa
T
T
Inagaki
J
J
Yamanaka
N
N
Ota
K
K
D000368:Aged; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
D004317:Doxorubicin; C010013:adriamycinol