Faculty Collaboration Database

Acetaminophen-associated hepatic injury: evaluation of acetaminophen protein adducts in children and adolescents with acetaminophen overdose. Clin Pharmacol Ther 2008 Dec;84(6):684-90

Date

10/17/2008

Pubmed ID

18923390

Pubmed Central ID

PMC2929246

DOI

10.1038/clpt.2008.190

Scopus ID

2-s2.0-56549091903 (requires institutional sign-in at Scopus site)   63 Citations

Abstract

Acetaminophen protein adducts (APAP adducts) were quantified in 157 adolescents and children presenting at eight pediatric hospitals with the chief complaint of APAP overdose. Two of the patients required liver transplantation, whereas all the others recovered spontaneously. Peak APAP adducts correlated with peak hepatic transaminase values, time-to-treatment with N-acetylcysteine (NAC), and risk determination per the Rumack-Matthews nomogram. A population pharmacokinetic analysis (NONMEM) was performed with post hoc empiric Bayesian estimates determined for the elimination rate constants (k(e)), elimination half-lives (t(1/2)), and maximum concentration of adducts (C(max)) of the subjects. The mean (+/-SD)k(e) and half-life were 0.486 +/- 0.084 days(-1) and 1.47+/- 0.30 days, respectively, and the C(max) was 1.2 (+/-2.92) nmol/ml serum. The model-derived, predicted adduct value at 48 h (Adduct 48) correlated with adductC(max), adduct T(max), Rumack-Matthews risk determination, peak aspartate aminotransferase (AST), and peak alanine aminotransferase (ALT). The pharmacokinetics and clinical correlates of APAP adducts in pediatric and adolescent patients with APAP overdose support the need for a further examination of the role of APAP adducts as clinically relevant and specific biomarkers of APAP toxicity.

Author List

James LP, Capparelli EV, Simpson PM, Letzig L, Roberts D, Hinson JA, Kearns GL, Blumer JL, Sullivan JE, Network of Pediatric Pharmacology Research Units, National Institutes of Child Health and Human Development

Author

Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetaminophen
Adolescent
Alanine Transaminase
Aspartate Aminotransferases
Bayes Theorem
Biomarkers
Blood Chemical Analysis
Chemical and Drug Induced Liver Injury
Child
Child, Preschool
Cohort Studies
Drug Compounding
Drug Overdose
Female
Half-Life
Humans
Male
Predictive Value of Tests
Probability
Risk Assessment
Statistics, Nonparametric