Acetaminophen Pharmacokinetics in Children With Nonalcoholic Fatty Liver Disease

OBJECTIVES: : The aim of the study was to evaluate UDP-glucuronyltransferase activity and the pharmacokinetics of a single oral dose of acetaminophen (APAP) in children with nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: : Twelve boys 10 to 17 years old with biopsy-proven NAFLD and 12 age- and sex-matched controls without NAFLD were recruited. Following administration of a single oral dose of APAP (5 mg/kg, maximum 325 mg), APAP and its glucuronide metabolite (APAP-G) were measured in plasma, urine, and sputum at various intervals up to 24 hours. The activity of UDP-glucuronyltransferase was estimated by the plasma ratio of APAP-G to APAP at 4 hours. RESULTS: : Following administration of APAP, children with NAFLD had significantly higher concentrations of APAP-G in serum (P = 0.0071) and urine (P = 0.0210) compared with controls. No significant differences in APAP pharmacokinetics parameters were observed between the 2 groups. CONCLUSIONS: : APAP glucuronidation is altered in children with fatty liver disease. Despite the altered disposition of this metabolite, the pharmacokinetics of a single 5 mg/kg dose of APAP is the same in children with NAFLD as in children with normal liver function.