Pharmacokinetics of doxorubicin and its active metabolite in patients with normal renal function and in patients on hemodialysis

Hiroshi Yoshida, Mitsuyoshi Goto, Atsuko Honda, Toshitaka Nabeshima, Takao Kumazawa, Jiro Inagaki, Naoki Yamanaka, Kazuo Ota

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 that achieved in non-HD patients. Careful attention should therefore be paid to HD patients receiving DOX.

Original languageEnglish
Pages (from-to)450-454
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume33
Issue number6
DOIs
Publication statusPublished - 01-11-1994

Fingerprint

Pharmacokinetics
Metabolites
Doxorubicin
Renal Dialysis
Kidney
Area Under Curve
adriamycinol
Rate constants

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Yoshida, Hiroshi ; Goto, Mitsuyoshi ; Honda, Atsuko ; Nabeshima, Toshitaka ; Kumazawa, Takao ; Inagaki, Jiro ; Yamanaka, Naoki ; Ota, Kazuo. / Pharmacokinetics of doxorubicin and its active metabolite in patients with normal renal function and in patients on hemodialysis. In: Cancer Chemotherapy and Pharmacology. 1994 ; Vol. 33, No. 6. pp. 450-454.
@article{9faec362bc0b4355aec0923a1e486dd4,
title = "Pharmacokinetics of doxorubicin and its active metabolite in patients with normal renal function and in patients on hemodialysis",
abstract = "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 that achieved in non-HD patients. Careful attention should therefore be paid to HD patients receiving DOX.",
author = "Hiroshi Yoshida and Mitsuyoshi Goto and Atsuko Honda and Toshitaka Nabeshima and Takao Kumazawa and Jiro Inagaki and Naoki Yamanaka and Kazuo Ota",
year = "1994",
month = "11",
day = "1",
doi = "10.1007/BF00686499",
language = "English",
volume = "33",
pages = "450--454",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "6",

}

Pharmacokinetics of doxorubicin and its active metabolite in patients with normal renal function and in patients on hemodialysis. / Yoshida, Hiroshi; Goto, Mitsuyoshi; Honda, Atsuko; Nabeshima, Toshitaka; Kumazawa, Takao; Inagaki, Jiro; Yamanaka, Naoki; Ota, Kazuo.

In: Cancer Chemotherapy and Pharmacology, Vol. 33, No. 6, 01.11.1994, p. 450-454.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pharmacokinetics of doxorubicin and its active metabolite in patients with normal renal function and in patients on hemodialysis

AU - Yoshida, Hiroshi

AU - Goto, Mitsuyoshi

AU - Honda, Atsuko

AU - Nabeshima, Toshitaka

AU - Kumazawa, Takao

AU - Inagaki, Jiro

AU - Yamanaka, Naoki

AU - Ota, Kazuo

PY - 1994/11/1

Y1 - 1994/11/1

N2 - 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 that achieved in non-HD patients. Careful attention should therefore be paid to HD patients receiving DOX.

AB - 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 that achieved in non-HD patients. Careful attention should therefore be paid to HD patients receiving DOX.

UR - http://www.scopus.com/inward/record.url?scp=0028326228&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028326228&partnerID=8YFLogxK

U2 - 10.1007/BF00686499

DO - 10.1007/BF00686499

M3 - Article

VL - 33

SP - 450

EP - 454

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 6

ER -