Propofol-induced cytochrome P450 inhibition: an in vitro and in vivo study in rats.
Propofol, a widely used anesthetic drug, is known to inhibit cytochrome P450 activities in vitro. The goal of this study was to compare cytochrome P450 activities in vitro and in vivo in presence of propofol. In vitro (liver microsomes and freshly isolated hepatocytes), cytochrome P450 IA2 and IIB1 activities were measured as the production of resorufin from ethoxy- and pentoxyresorufin, respectively, in presence of various concentrations of propofol. In vivo, cytochrome P450 activities were assessed as the production of 13CO2 from 13C-aminopyrine injected intravenously, during acute administration or after chronic treatment. In vitro results confirmed the dose-dependent inhibitory effect of propofol on cytochrome P450 activities, both on liver microsomes and isolated hepatocytes. In vivo, the acute administration of propofol induced a significant decrease of 13C-aminopyrine metabolism. Chronic treatment with propofol induced a significant inhibition of 13C-aminopyrine metabolism only after 2 weeks. No enzyme induction was observed. In conclusion, our results demonstrate that propofol inhibits cytochrome P450 also in vivo. Drug interactions may thus occur during propofol administration.
Gemayel
J
J
CNRS UMR 5578, Laboratoire de Physiologie Lyon-Nord, Université Claude Bernard, France.
Géloën
A
A
Mion
F
F
D000632:Aminopyrine / Q000378:metabolism; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002245:Carbon Dioxide / Q000032:analysis; D002247:Carbon Isotopes; D002470:Cell Survival; D065607:Cytochrome P-450 Enzyme Inhibitors; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology*; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D007700:Kinetics; D008099:Liver / Q000166:cytology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018686:Anesthetics, Intravenous; D002247:Carbon Isotopes; D065607:Cytochrome P-450 Enzyme Inhibitors; D000632:Aminopyrine; D002245:Carbon Dioxide; D015742:Propofol; D010634:Phenobarbital