Acetaminophen pharmacokinetics in children with nonalcoholic fatty liver disease.
OBJECTIVE
: 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).


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.
Department of Pediatrics, University of California, San Diego, USA.
Nicole J
NJ
Barshop
Edmund V
EV
Capparelli
Claude B
CB
Sirlin
Jeffrey B
JB
Schwimmer
Joel E
JE
Lavine
D000082:Acetaminophen / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D005234:Fatty Liver / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000503:physiopathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D018709:Statistics, Nonparametric
D000082:Acetaminophen; C037386:acetaminophen glucuronide; D014453:Glucuronosyltransferase
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