title: The influence of anesthetic agents on rat hepatic cytochromes P450 in vivo.
abstract: The objective of this study was to identify which anesthetics when used acutely will affect cytochrome P450 (CYP) activity in male Sprague-Dawley rats in vivo. The anesthetics tested were fentanyl citrate, alpha-chloralose, ketamine, urethane (ethyl carbamate), halothane, and ether. CO2 anesthesia was used as the control comparator. Theophylline was used as a probe for CYP1A activity, phenobarbital for CYP2B/2C, flecainide for CYP2D1, and ethosuximide for CYP3A activity. All probes were administered via tail vein injection after anesthetic-induced loss of the righting reflex. Single sample probe clearances were estimated, and used as an index of CYP activity. Fentanyl citrate, alpha-chloralose, halothane, and ether did not have statistically significant effects on any of the CYP activities. Ketamine did not significantly affect CYP1 or CYP2B/2C activity. However, it decreased the clearance of flecainide (i.e. CYP2D1 activity) by 13.4% (p < 0.001) and the clearance of ethosuximide (i.e. CYP3A activity) by 17.6% (p < 0.0001). Urethane increased the clearance of theophylline by 91.5% (p < 0.0001), and decreased the clearance of ethosuximide by 40.5% (p < 0.0001) though it did not affect CYP2B/2C or CYP2D1 activities significantly. From this data, we conclude that a single dose of ketamine mildly inhibits the activity of CYP2D1 and CYP3A, and a single dose of urethane strongly inhibits CYP3A but increases CYP1A activity.
authors.affiliation: University of Toledo College of Pharmacy, Department of Pharmacology, Ohio 43606, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Loch
authors.forename: J
authors.initials: J
authors.lastname: Potter
authors.forename: K A
authors.initials: KA
authors.lastname: Bachmann
mesh_terms: D000704:Analysis of Variance; D018681:Anesthetics, General / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002698:Chloralose / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D004986:Ether / Q000494:pharmacology; D005283:Fentanyl / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014520:Urethane / Q000494:pharmacology
chemical_list: D018681:Anesthetics, General; D004986:Ether; D002698:Chloralose; D014520:Urethane; D007649:Ketamine; D003577:Cytochrome P-450 Enzyme System; D005283:Fentanyl; D006221:Halothane