Medico

NIH Public Access
Author Manuscript
J Pediatr Gastroenterol Nutr. Author manuscript; available in PMC 2012 February 1.

NIH-PA Author Manuscript

Published in final edited form as:
J Pediatr Gastroenterol Nutr. 2011 February ; 52(2): 198–202. doi:10.1097/MPG.0b013e3181f9b3a0.

Acetaminophen Pharmacokinetics in Children with Nonalcoholic
Fatty Liver Disease
Nicole J. Barshop, MD1,Edmund V. Capparelli, PharmD1, Claude B. Sirlin, MD2, Jeffrey B.
Schwimmer, MD1, and Joel E Lavine, MD PhD1
1Department of Pediatrics, University of California, San Diego, San Diego, CA and Rady
Children’s Hospital, San Diego
2Department

of Radiology, University of California, San Diego, San Diego, CA

Abstract
NIH-PA Author Manuscript

Objectives—To evaluate UDP-glucuronyltransferase (UGT)activity and the pharmacokinetics
of a single oral dose of acetaminophen (APAP) in children with non-alcoholic fatty liver disease
(NAFLD).
Methods—Twelve boys 10–17 years old with biopsy-proven NAFLD and 12 age and gendermatched 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 UGT
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=.0071) and urine (p=.0210) compared to controls. No
significant differences in APAP pharmacokineticsparameters were observed between the two
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.
Keywords

NIH-PA Author Manuscript

nonalcoholic fatty liver disease; nonalcoholicsteatohepatitis; acetaminophen; UDPglucuronyltransferase; pharmacokinetics; pediatrics

INTRODUCTION
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in
children. NAFLD is a clinico-pathological diagnosis characterized by the accumulation of
macrovesicular fat in hepatocytes in the absence of alcohol consumption. NAFLD
encompasses a spectrum of ofhistopathological features ranging from simple steatosis to

Correspondence: Dr. Joel Lavine, Columbia University, 3959 Broadway, CHN7-702, New York, New York 10032, Phone (212)
304-5533, Fax (212) 342-4779, jl3553@columbia.edu.
Reprint Request Author: Dr. Joel Lavine
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to ourcustomers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of
the resulting proof before it is published in its final citable form. Please note that during the production process errors may be
discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Barshop et al.

Page 2NIH-PA Author Manuscript

steatosis with inflammation, ballooning degeneration and pericellular fibrosis (nonalcoholic
steatohepatitis, NASH) to cirrhosis. The existing population-based prevalence studies
suggest that NAFLD is a global problem with reports published in North and South
America, Europe, Australia and Asia (1). However, since NAFLD is diagnosed by liver
biopsy, it is hard toestimate the prevalence in children in a population-based study. In a
community representative autopsy study which was based on liver histology conducted from
1993 to 2003, the standardized prevalence of fatty liver disease in children aged 2 to 19
years was estimated at 9.6% (2).

NIH-PA Author Manuscript

The detailed effects of intra-hepatocellular lipid accumulation on hepatic function are...