Cytochrome P-450 activity is differentially altered in severely injured patients.
OBJECTIVE
To assess whether changes in cytochrome P-450 (CYP) activity of specific CYP enzymes occur in severely injured patients and to assess changes in CYP activity during recovery.


METHODS
Prospective clinical study.


METHODS
University-affiliated, level I trauma center and trauma critical care unit.


METHODS
Twenty-three multiply injured patients admitted to a trauma critical care unit were compared with healthy volunteers.


METHODS
CYP metabolizing activity was assessed using the probe drugs mephenytoin (CYP-2C19), chlorzoxazone (CYP-2E1), dapsone (multiple CYP enzymes), and flurbiprofen (CYP-2C9).


RESULTS
Mephenytoin metabolism was profoundly suppressed after injury and increased during postinjury recovery, whereas chlorzoxazone metabolism was suppressed to a lesser degree. Measures of dapsone and flurbiprofen metabolism were elevated throughout the study. Chlorzoxazone and mephenytoin metabolism correlated with the multiple organ dysfunction score and with the multiple organ failure score.


CONCLUSIONS
CYP isoform activity is differentially altered by shock and trauma in injured patients. The metabolic activity of selected CYP isoforms may have potential for evaluating acute hepatic dysfunction in critically ill trauma patients.
Harbrecht
Brian G
BG
Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Frye
Reginald F
RF
Zenati
Mazen S
MS
Branch
Robert A
RA
Peitzman
Andrew B
AB
D015415:Biomarkers; D016022:Case-Control Studies; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D016014:Linear Models; D017093:Liver Failure / Q000175:diagnosis / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000175:diagnosis / Q000378:metabolism; D011446:Prospective Studies; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D014947:Wounds and Injuries / Q000378:metabolism*
D015415:Biomarkers; D003577:Cytochrome P-450 Enzyme System