The effect of oxygen on propofol-induced inhibition of microsomal cytochrome P450 3A4

We have shown previously that both hypoxia and propofol may inhibit the met abolism of midazolam. We now wished to see whether there was any additive o r synergistic effect when they occurred together. Microsomes were incubated with 20 mu m midazolam for 60 min, and propofol 0, 50, 100 or 1000 mu M wa s added. Incubates were further subdivided so that the environment containe d 0, 10, 21 or 70% oxygen. The results confirmed our earlier study showing that propofol only had a significant inhibitory effect at a concentration g reater than that seen clinically (1000 mu M). Anoxia was the only environme nt in which significant depression of the metabolism of midazolam occurred at all concentrations of propofol. This reduced it to almost zero. Post hoc analysis of the data showed that, with the greatest concentration of propo fol (1000 mu M), there was increasing inhibition of metabolism of midazolam with increases of oxygen from 10 to 70%.