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Cytochrome P-450 activity is differentially altered in severely injured patients

Harbrecht, Brian G. MD; Frye, Reginald F. P.D; Zenati, Mazen S. MD, MPH; Branch, Robert A. MD; Peitzman, Andrew B. MD

doi: 10.1097/01.CCM.0000155989.54344.E0
Clinical Investigations
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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.

Design: Prospective clinical study.

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

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

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

Measurements and Main 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.

From the Department of Surgery (BGH, MSZ, ABP) and Department of Pharmacology (RFF, RAB), University of Pittsburgh, Pittsburgh, PA; and the College of Pharmacy (RFF), University of Florida, Gainesville, FL

Supported, in part, by grants DK55664 (BGH), DK59519 (RAB), 5M01RR00056 (RAB), and P50 GM53789 (BGH) from the National Institutes of Health, Bethesda, MD.

© 2005 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins