Premium
What changes drug metabolism in critically ill patients?—II Serum inhibits the metabolism of midazolam in human microsomes
Author(s) -
PARK G. R.,
MILLER E.,
NAVAPURKAR V.
Publication year - 1996
Publication title -
anaesthesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.839
H-Index - 117
eISSN - 1365-2044
pISSN - 0003-2409
DOI - 10.1111/j.1365-2044.1996.tb07646.x
Subject(s) - midazolam , medicine , microsome , drug metabolism , critically ill , metabolism , cytochrome p450 , drug , pharmacology , cyp3a4 , cytochrome , enzyme , biochemistry , chemistry , sedation
Summary Serum samples from fire 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.