Drug metabolism and disposition : the biological fate of chemicals
-
Drug Metab. Dispos. · Aug 2009
Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure.
Acetaminophen (APAP)-induced liver toxicity occurs with formation of APAP-protein adducts. These adducts are formed by hepatic metabolism of APAP to N-acetyl-p-benzoquinone imine, which covalently binds to hepatic proteins as 3-(cystein-S-yl)-APAP adducts. Adducts are released into blood during hepatocyte lysis. ⋯ The mean elimination rate constant and elimination half-life were 0.42 +/- 0.09 days(-1) and 1.72 +/- 0.34 days, respectively, and estimates from the population model were in strong agreement with these data. Adducts were detected in some patient samples 12 days post-ingestion. The persistence and specificity of APAP-protein adducts as correlates of toxicity support their use as specific biomarkers of APAP toxicity in patients with acute liver injury.