A COMPARISON OF THE INHIBITORY EFFECTS OF 4 VOLATILE ANESTHETICS ON THE METABOLISM OF CHLORZOXAZONE, A SUBSTRATE FOR CYP2E1, IN RABBITS

Background: Halothane inhibits in vitro and in vivo activity of cytoch rome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthet ics besides halothane, and most of them are defluorinated by CYP2E1. I t is unclear whether other fluorinated anaesthetics inhibit the in viv o activity of CYP2E1. Methods: We compared the inhibitory effects of t herapeutic concentrations of four inhalational anaesthetics, halothane , enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation. Results: All four inhalat ional anaesthetics decreased arterial blood pressure and increased pla sma chlorzoxazone concentration. However, no significant differences i n the plasma chlorzoxazone concentration were found between the four a naesthetics. The estimated chlorzoxazone clearance increased after beg inning inhalation with all four agents, but no significant difference in clearance was noted between agents. Conclusions: At therapeutic con centrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even tho ugh their chemical characteristics and extent of hepatic metabolism di ffer considerably.