What changes drug metabolism in critically ill patients .2. Serum inhibits the metabolism of midazolam in human microsomes

Serum samples from five critically ill patients were incubated with microsomes prepared from three human livers. The activity of cytochrome P450 3A4 was assessed by measuring the disappearance of midazolam and the appearance of 1-hydroxy midazolam in the incubates. Significant inhibition of the ability of this enzyme to metabolise midazolam was seen. This occurred in incubates containing serum samples from critically ill patients and not in those containing serum from two normal volunteers. The mechanism of this inhibition is unknown, but several possibilities are discussed.