Open AccessAcetaminophen Pharmacokinetics in Children With Nonalcoholic Fatty Liver Disease
Author(s) -
Barshop Nicole J,
Capparelli Edmund V,
Sirlin Claude B,
Schwimmer Jeffrey B,
Lavine Joel E
Publication year - 2011
Publication title -
journal of pediatric gastroenterology and nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 131
eISSN - 1536-4801
pISSN - 0277-2116
DOI - 10.1097/mpg.0b013e3181f9b3a0
Subject(s) - medicine , acetaminophen , pharmacokinetics , nonalcoholic fatty liver disease , glucuronidation , urine , metabolite , liver disease , oral administration , gastroenterology , pharmacology , endocrinology , fatty liver , disease , microsome , biochemistry , enzyme , chemistry
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.