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 P45 0 activities in vitro. The goal of this study was to compare cytochrome P45 0 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 pe ntoxyresorufin, respectively, in presence of various concentrations of prop ofol. In vivo, cytochrome P450 activities were assessed as the production o f (CO2)-C-13 from C-13-aminopyrine injected intravenously, during acute adm inistration or after chronic treatment. In vitro results confirmed the dose -dependent inhibitory effect of propofol on cytochrome P450 activities, bot h on liver microsomes and isolated hepatocytes. In vivo, the acute administ ration of propofol induced a significant decrease of C-13-aminopyrine metab olism. Chronic treatment with propofol induced a significant inhibition of C-13-aminopyrine metabolism only after 2 weeks. No enzyme induction was obs erved. In conclusion, our results demonstrate that propofol inhibits cytoch rome P450 also in vivo. Drug interactions may thus occur during propofol ad ministration. (C) 2001 Elsevier Science Inc. All rights reserved.