HUMAN CYTOCHROME-P450 MONOOXYGENASE SYSTEM IS SUPPRESSED BY PROPOFOL

We have studied the effect of propofol on the cytochrome P450-dependen t mono-oxygenase system in human liver microsomes by assaying mono-oxy genase activities toward specific cytochrome P450 isoform test substra tes, aniline, 7-ethoxycoumarin, benzphetamine and benzo(a) pyrene. Pro pofol inhibited benzo(a) pyrene hydroxylation to a greater extent than the oxidative metabolism of the other test substrates, even at 0.05 m mol litre(-1). The degrees of inhibition of benzphetamine N-demethylat ion and 7-ethoxycoumarin O-de-ethylation were similar, while aniline h ydroxylation was least affected by propofol. Spectral analysis showed that propofol competed with carbon monoxide for binding to the haem mo iety of haemoprotein in the P450 enzyme. The variable inhibition obser ved may be caused by the differential binding of propofol to P450 isof orms. Propofol 0.05-1.0 mmol litre(-1) exhibited a concentration-depen dent inhibitory effect on human cytochrome P450 2E1, 2B1 and 1A1. Thes e inhibitory actions of propofol on human liver microsomal enzymes in vitro suggest that potential drug interactions may exist between propo fol and other drugs administered clinically.