Halothane inhalation inhibits the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Tomonori Tateishi, Minoru Watanabe, Hironori Nakura, Masami Tanaka, Toshio Kumai, Tadashi Aoki, Shinichi Kobayashi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We demonstrated the inhibitory effect of halothane (HAL) inhalation on the metabolism of chlorzoxazone (CZZ), a substrate for CYP2E1, in a bolus and a continuous injection study in rabbits receiving artificial ventilation. In a bolus injection study, the inhalation of 1.0% HAL significantly increased the half-line and the area under the curve and decreased the clearance of CZZ compared with those variables in midazolam administration. In a continuous injection study, the effect of various concentrations of inhaled HAL on plasma CZZ concentration at steady state was compared. Systolic and diastolic arterial blood pressure were decreased dose-dependently after 0.5%, 1.0%, or 2.0% HAL was inhaled. Although the plasma concentration of CZZ was increased 2.5-fold later 3 h of HAL inhalation, there was no significant difference in mean plasma concentrations among the groups treated with 0.5%, 1.0%, or 2.0% HAL. In contrast, the plasma concentration of lidocaine, a substrate for CYP3A, remained unchanged after 1.0% HAL was inhaled. These results suggest that general anesthesia obtained with HAL inhalation will affect the metabolism of drugs administered concomitantly when the drug is a substrate for CYP2E1.

Original languageEnglish
Pages (from-to)199-203
Number of pages5
JournalAnesthesia and Analgesia
Volume85
Issue number1
DOIs
Publication statusPublished - 1997
Externally publishedYes

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Chlorzoxazone
Cytochrome P-450 CYP2E1
Halothane
Inhalation
Rabbits
Injections
Cytochrome P-450 CYP3A
Midazolam
Lidocaine
Pharmaceutical Preparations
General Anesthesia
Area Under Curve
Arterial Pressure

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Halothane inhalation inhibits the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits. / Tateishi, Tomonori; Watanabe, Minoru; Nakura, Hironori; Tanaka, Masami; Kumai, Toshio; Aoki, Tadashi; Kobayashi, Shinichi.

In: Anesthesia and Analgesia, Vol. 85, No. 1, 1997, p. 199-203.

Research output: Contribution to journalArticle

Tateishi, Tomonori ; Watanabe, Minoru ; Nakura, Hironori ; Tanaka, Masami ; Kumai, Toshio ; Aoki, Tadashi ; Kobayashi, Shinichi. / Halothane inhalation inhibits the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits. In: Anesthesia and Analgesia. 1997 ; Vol. 85, No. 1. pp. 199-203.
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