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 mi crosomes 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 in hibition of the ability of this enzyme to metabolise midazolam was see n. This occurred in incubates containing serum samples from critically ill patients and not in those containing serum from two normal volunt eers. The mechanism of this inhibition is unknown, but several possibi lities are discussed.