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The effect of oxygen on propofol‐induced inhibition of microsomal cytochrome P450 3A4
Author(s) -
Miller E.,
Park G. R.
Publication year - 1999
Publication title -
anaesthesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.839
H-Index - 117
eISSN - 1365-2044
pISSN - 0003-2409
DOI - 10.1046/j.1365-2044.1999.00747.x
Subject(s) - propofol , midazolam , medicine , oxygen , microsome , metabolism , hypoxia (environmental) , pharmacology , cytochrome p450 , anesthesia , in vitro , biochemistry , sedation , biology , chemistry , organic chemistry
We have shown previously that both hypoxia and propofol may inhibit the metabolism of midazolam. We now wished to see whether there was any additive or synergistic effect when they occurred together. Microsomes were incubated with 20 μm midazolam for 60 min, and propofol 0, 50, 100 or 1000 μ M was added. Incubates were further subdivided so that the environment contained 0, 10, 21 or 70% oxygen. The results confirmed our earlier study showing that propofol only had a significant inhibitory effect at a concentration greater than that seen clinically (1000 μ M ). Anoxia was the only environment 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 propofol (1000 μ M ), there was increasing inhibition of metabolism of midazolam with increases of oxygen from 10 to 70%.