Endogenous uremic substances are not involved in the reduced hepatic extraction of metoprolol in bilateral ureter-ligated rats.

Masato Taguchi; Misato Urai; Shigehiro Taira; Hiroko Tanabe; Yukiya Hashimoto

doi:10.2133/dmpk.21.156

Endogenous uremic substances are not involved in the reduced hepatic extraction of metoprolol in bilateral ureter-ligated rats.

Masato Taguchi^*, Misato Urai, Shigehiro Taira, Hiroko Tanabe, Yukiya Hashimoto

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

The hepatic extraction of metoprolol is reduced in rats with bilateral ureter ligation (BUL)-induced renal failure. The aim of the present study was to evaluate the effect of uremic substances on the hepatic metabolism of metoprolol in rats with BUL. The metabolic rate in the liver microsomes of BUL rats was similar to that in sham rats, and there was no significant difference between sham and BUL rats in the effect of the supernatant of liver homogenates on the metabolism. The rate of metabolism in the liver microsomes in the presence of the plasma of BUL rats was also similar to that in the presence of the plasma of sham rats. These findings indicated that uremic substances which accumulate in BUL rats do not directly inhibit the activity of CYP2D2, which is responsible for the metabolism of metoprolol in the rat liver.

Original language	English
Pages (from-to)	156-164
Number of pages	9
Journal	Drug Metabolism and Pharmacokinetics
Volume	21
Issue number	2
DOIs	https://doi.org/10.2133/dmpk.21.156
State	Published - 2006/04

ASJC Scopus subject areas

Pharmacology
Pharmaceutical Science
Pharmacology (medical)

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@article{193fcdbaa86a4c60b690aa7b9206181f,

title = "Endogenous uremic substances are not involved in the reduced hepatic extraction of metoprolol in bilateral ureter-ligated rats.",

abstract = "The hepatic extraction of metoprolol is reduced in rats with bilateral ureter ligation (BUL)-induced renal failure. The aim of the present study was to evaluate the effect of uremic substances on the hepatic metabolism of metoprolol in rats with BUL. The metabolic rate in the liver microsomes of BUL rats was similar to that in sham rats, and there was no significant difference between sham and BUL rats in the effect of the supernatant of liver homogenates on the metabolism. The rate of metabolism in the liver microsomes in the presence of the plasma of BUL rats was also similar to that in the presence of the plasma of sham rats. These findings indicated that uremic substances which accumulate in BUL rats do not directly inhibit the activity of CYP2D2, which is responsible for the metabolism of metoprolol in the rat liver.",

author = "Masato Taguchi and Misato Urai and Shigehiro Taira and Hiroko Tanabe and Yukiya Hashimoto",

note = "Funding Information: Acknowledgements: This work was supported in part by a Grant-in-Aid for Scientiˆc Research from the Japan Society for the Promotion of Sciences (JSPS) and The Nakatomi Foundation.",

year = "2006",

month = apr,

doi = "10.2133/dmpk.21.156",

language = "英語",

volume = "21",

pages = "156--164",

journal = "Drug Metabolism and Pharmacokinetics",

issn = "1347-4367",

publisher = "Japanese Society for the Study of Xenobiotics",

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TY - JOUR

T1 - Endogenous uremic substances are not involved in the reduced hepatic extraction of metoprolol in bilateral ureter-ligated rats.

AU - Taguchi, Masato

AU - Urai, Misato

AU - Taira, Shigehiro

AU - Tanabe, Hiroko

AU - Hashimoto, Yukiya

N1 - Funding Information: Acknowledgements: This work was supported in part by a Grant-in-Aid for Scientiˆc Research from the Japan Society for the Promotion of Sciences (JSPS) and The Nakatomi Foundation.

PY - 2006/4

Y1 - 2006/4

N2 - The hepatic extraction of metoprolol is reduced in rats with bilateral ureter ligation (BUL)-induced renal failure. The aim of the present study was to evaluate the effect of uremic substances on the hepatic metabolism of metoprolol in rats with BUL. The metabolic rate in the liver microsomes of BUL rats was similar to that in sham rats, and there was no significant difference between sham and BUL rats in the effect of the supernatant of liver homogenates on the metabolism. The rate of metabolism in the liver microsomes in the presence of the plasma of BUL rats was also similar to that in the presence of the plasma of sham rats. These findings indicated that uremic substances which accumulate in BUL rats do not directly inhibit the activity of CYP2D2, which is responsible for the metabolism of metoprolol in the rat liver.

AB - The hepatic extraction of metoprolol is reduced in rats with bilateral ureter ligation (BUL)-induced renal failure. The aim of the present study was to evaluate the effect of uremic substances on the hepatic metabolism of metoprolol in rats with BUL. The metabolic rate in the liver microsomes of BUL rats was similar to that in sham rats, and there was no significant difference between sham and BUL rats in the effect of the supernatant of liver homogenates on the metabolism. The rate of metabolism in the liver microsomes in the presence of the plasma of BUL rats was also similar to that in the presence of the plasma of sham rats. These findings indicated that uremic substances which accumulate in BUL rats do not directly inhibit the activity of CYP2D2, which is responsible for the metabolism of metoprolol in the rat liver.

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U2 - 10.2133/dmpk.21.156

DO - 10.2133/dmpk.21.156

M3 - 学術論文

C2 - 16702736

AN - SCOPUS:33745007154

SN - 1347-4367

VL - 21

SP - 156

EP - 164

JO - Drug Metabolism and Pharmacokinetics

JF - Drug Metabolism and Pharmacokinetics

IS - 2

ER -

Endogenous uremic substances are not involved in the reduced hepatic extraction of metoprolol in bilateral ureter-ligated rats.

Abstract

ASJC Scopus subject areas

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