التفاصيل البيبلوغرافية
| العنوان: |
Circulating acetaminophen metabolites are toxicokinetic biomarkers of acute liver injury. |
| المؤلفون: |
Vliegenthart, ADB, Kimmitt, RA, Seymour, JH, Homer, NZ, Clarke, JI, Eddleston, M, Gray, A, Wood, DM, Dargan, PI, Cooper, JG, Antoine, DJ, Webb, DJ, Lewis, SC, Bateman, DN, Dear, JW |
| المصدر: |
Clinical Pharmacology & Therapeutics; Apr2017, Vol. 101 Issue 4, p531-540, 10p |
| مصطلحات موضوعية: |
ACETAMINOPHEN, BIOMARKERS, THERAPEUTICS, LIVER injuries, DRUG side effects, METABOLITES |
| مستخلص: |
Acetaminophen (paracetamol-APAP) is the most common cause of drug-induced liver injury in the Western world. Reactive metabolite production by cytochrome P450 enzymes (CYP-metabolites) causes hepatotoxicity. We explored the toxicokinetics of human circulating APAP metabolites following overdose. Plasma from patients treated with acetylcysteine (NAC) for a single APAP overdose was analyzed from discovery ( n = 116) and validation ( n = 150) patient cohorts. In the discovery cohort, patients who developed acute liver injury (ALI) had higher CYP-metabolites than those without ALI. Receiver operator curve (ROC) analysis demonstrated that at hospital presentation CYP-metabolites were more sensitive/specific for ALI than alanine aminotransferase (ALT) activity and APAP concentration (optimal CYP-metabolite receiver operating characteristic area under the curve (ROC-AUC): 0.91 (95% confidence interval (CI) 0.83-0.98); ALT ROC-AUC: 0.67 (0.50-0.84); APAP ROC-AUC: 0.50 (0.33-0.67)). This enhanced sensitivity/specificity was replicated in the validation cohort. Circulating CYP-metabolites stratify patients by risk of liver injury prior to starting NAC. With development, APAP metabolites have potential utility in stratified trials and for refinement of clinical decision-making. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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