Acetaminophen Pharmacokinetics in Children With Nonalcoholic Fatty Liver Disease

作者：Barshop Nicole J; Capparelli Edmund V; Sirlin Claude B; Schwimmer Jeffrey B; Lavine Joel E^*

来源：Journal of Pediatric Gastroenterology and Nutrition, 2011, 52(2): 198-202.

DOI：10.1097/MPG.0b013e3181f9b3a0

• acetaminophen
• nonalcoholic fatty liver disease
• nonalcoholic steatohepatitis
• pediatrics
• pharmacokinetics
• UDP-glucuronyltransferase

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 (5mg/kg, maximum 325mg), 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.

• 出版日期2011-2