A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits.
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.
Tateishi
T
T
Department of Pharmacology, St. Marianna University School of Medicine, Kanagawa, Japan.
Watanabe
M
M
Nakura
H
H
Tanaka
M
M
Kumai
T
T
Aoki
T
T
Kobayashi
S
S
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002753:Chlorzoxazone / Q000493:pharmacokinetics*; D019392:Cytochrome P-450 CYP2E1 / Q000502:physiology; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004347:Drug Interactions; D008297:Male; D009125:Muscle Relaxants, Central / Q000493:pharmacokinetics*; D011817:Rabbits
D018685:Anesthetics, Inhalation; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D009125:Muscle Relaxants, Central; D019392:Cytochrome P-450 CYP2E1; D002753:Chlorzoxazone