Human cytochrome P450 mono-oxygenase system is suppressed by propofol

We have studied the effect of propofol on the cytochrome P450-dependentmono-oxygenase system in human liver microsomes by assayingmono-oxygenase activities toward specific cytochrome P450 isoformtest substrates, aniline, 7-ethoxycoumarin, benzphetamine andbenzo(a) pyrene. Propofol inhibited benzo(a)pyrene hydroxylationto a greater extent than the oxidative metabolism of the othertest substrates, even at 0.05 mmol litre^–1 The degreesof inhibition of benzphetamine N-demethylation and 7-ethoxy-coumarinO-de-ethylation were similar, while aniline hydroxylation wasleast affected by propofol. Spectral analysis showed that propofolcompeted with carbon monoxide for binding to the haem moietyof haemoprotein in the P450 enzyme. The variable inhibitionobserved may be caused by the differential binding of propofolto P450 isoforms. Propofol 0.05–1.0 mmol litre^–1exhibited a concentration-dependent inhibitory effect on humancytochrome P450 2E1, 2B1 and 1A1. These inhibitory actions ofpropofol on human liver microsomal enzymes in vitro suggestthat potential drug interactions may exist between propofoland other drugs administered clinically. (Br. J. Anaesth. 1995;74: 558–562)