THE INFLUENCE OF ANESTHETIC AGENTS ON RAT HEPATIC CYTOCHROMES P450 IN-VIVO

The objective of this study was to identify which anesthetics when use d acutely will affect cytochrome P450 (CYP) activity in male Sprague-D awley rats in vivo. The anesthetics tested were fentanyl citrate, alph a-chloralose, ketamine, urethane (ethyl carbamate), halothane, and eth er. CO2 anesthesia was used as the control comparator. Theophylline wa s used as a probe for CYP1A activity, phenobarbital for CYP2B/2C, flec ainide for CYP2D1, and ethosuximide for CYP3A activity. All probes wer e administered via tail vein injection after anesthetic-induced loss o f the righting reflex. Single sample probe clearances were estimated, and used as an index of CYP activity. Fentanyl citrate, alpha-chloralo se, halothane, and ether did not have statistically significant effect s on any of the CYP activities. Ketamine did not significantly affect CYP1 or CYP2B/2C activity. However, it decreased the clearance of flec ainide (i.e. CYP2D1 activity) by 13.4% (p < 0.001) and the clearance o f ethosuximide (i.e. CYP3A activity) by 17.6% (p < 0.0001). Urethane i ncreased the clearance of theophylline by 91.5% (p < 0.0001), and decr eased the clearance of ethosuximide by 40.5% (p < 0.0001) though it di d not affect CYP2B/2C or CYP2D1 activities significantly. From this da ta, we conclude that a single dose of ketamine mildly inhibits the act ivity of CYP2D1 and CYP3A, and a single dose of urethane strongly inhi bits CYP3A but increases CYP1A activity.