A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

T. Tateishi, M. Watanabe, Hironori Nakura, M. Tanaka, T. Kumai, T. Aoki, S. Kobayashi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (cYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1. Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation. Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents. Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.

Original languageEnglish
Pages (from-to)1028-1032
Number of pages5
JournalActa Anaesthesiologica Scandinavica
Volume42
Issue number9
Publication statusPublished - 1998
Externally publishedYes

Fingerprint

Chlorzoxazone
Cytochrome P-450 CYP2E1
Anesthetics
Rabbits
Halothane
Enflurane
Isoflurane
Therapeutic Uses
Cytochrome P-450 Enzyme System
Inhalation
Arterial Pressure
Liver

Keywords

  • Chlorzoxazone
  • Drug- interaction
  • Enflurane
  • Halothane
  • Isoflurane
  • Rabbits
  • Sevoflurane

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits. / Tateishi, T.; Watanabe, M.; Nakura, Hironori; Tanaka, M.; Kumai, T.; Aoki, T.; Kobayashi, S.

In: Acta Anaesthesiologica Scandinavica, Vol. 42, No. 9, 1998, p. 1028-1032.

Research output: Contribution to journalArticle

@article{e9f0f2eba13a429fb74d89829ebf0d8d,
title = "A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits",
abstract = "Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (cYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1. Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation. Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents. Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.",
keywords = "Chlorzoxazone, Drug- interaction, Enflurane, Halothane, Isoflurane, Rabbits, Sevoflurane",
author = "T. Tateishi and M. Watanabe and Hironori Nakura and M. Tanaka and T. Kumai and T. Aoki and S. Kobayashi",
year = "1998",
language = "English",
volume = "42",
pages = "1028--1032",
journal = "Acta Anaesthesiologica Scandinavica",
issn = "0001-5172",
publisher = "Blackwell Munksgaard",
number = "9",

}

TY - JOUR

T1 - A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

AU - Tateishi, T.

AU - Watanabe, M.

AU - Nakura, Hironori

AU - Tanaka, M.

AU - Kumai, T.

AU - Aoki, T.

AU - Kobayashi, S.

PY - 1998

Y1 - 1998

N2 - Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (cYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1. Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation. Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents. Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.

AB - Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (cYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1. Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation. Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents. Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.

KW - Chlorzoxazone

KW - Drug- interaction

KW - Enflurane

KW - Halothane

KW - Isoflurane

KW - Rabbits

KW - Sevoflurane

UR - http://www.scopus.com/inward/record.url?scp=0031755283&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031755283&partnerID=8YFLogxK

M3 - Article

VL - 42

SP - 1028

EP - 1032

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

SN - 0001-5172

IS - 9

ER -