The influence of anesthetic agents on rat hepatic cytochromes P450 in vivo

Pharmacology. 1995 Mar;50(3):146-53. doi: 10.1159/000139276.


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.

MeSH terms

  • Analysis of Variance
  • Anesthetics, General / blood
  • Anesthetics, General / pharmacology*
  • Animals
  • Chloralose / pharmacology
  • Cytochrome P-450 Enzyme System / drug effects*
  • Ether / pharmacology
  • Fentanyl / pharmacology
  • Halothane / pharmacology
  • Ketamine / pharmacology
  • Liver / drug effects*
  • Liver / enzymology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Urethane / pharmacology


  • Anesthetics, General
  • Ether
  • Chloralose
  • Urethane
  • Ketamine
  • Cytochrome P-450 Enzyme System
  • Fentanyl
  • Halothane