Impact of malnourishment on the pharmacokinetics of acetaminophen and susceptibility to acetaminophen hepatotoxicity

BACKGROUND: Acetaminophen hepatotoxicity is thought to be primarily caused by formation of the specific reactive metabolite N‐acetyl‐para‐benzo‐quinone imine (NAPQI). Malnourished individuals are at increased risk of acetaminophen‐related hepatotoxicity. We report a case of low acetaminophen clearance in a severely underweight young woman, and elaborate on the possible effects of malnutrition on the total clearance of acetaminophen as well as on the separate contributions of the different metabolic pathways. CASE REPORT: An 18‐year‐old Caucasian woman weighing 43 kg with a history of eating disorder‐related hospital admissions presented at the emergency department after having ingested 33 tablets of acetaminophen 500 mg two hours earlier. She then received intravenous N‐acetylcysteine for 33 h. Nine hours after ingestion, the acetaminophen elimination half‐life (t½) was estimated to be >100 h. DISCUSSION: While decreased total acetaminophen clearance (twofold) due to malnutrition has been reported in literature, the extremely low clearance in this specific patient cannot be explained. Malnourished individuals generally have reduced antioxidant reserves, coinciding with a shift in metabolic routes toward oxidative metabolism. This may result in increased formation of NAPQI and reduced neutralizing capacity, thereby increasing the risk of acetaminophen‐induced hepatotoxicity. Evidence for this observation can be found in animal and to a lesser extent in human studies.