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Evaluating human liver reserve function by measuring serum concentrations of phenacetin and its metabolites
Author(s) -
XIONG Wen Jian,
JIN Hui,
LI Shui Jun,
JIN Jia Chen,
JI Bei Na,
YU Chen
Publication year - 2010
Publication title -
journal of digestive diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 51
eISSN - 1751-2980
pISSN - 1751-2972
DOI - 10.1111/j.1751-2980.2010.00463.x
Subject(s) - phenacetin , medicine , acetaminophen , volunteer , cirrhosis , glucuronide , metabolite , liver function , gastroenterology , pharmacology , biology , agronomy
OBJECTIVES: To evaluate human liver reserve function (LRF) by a simple and efficient method for measuring serum concentrations of phenacetin and its metabolites. METHODS: Overall 20 patients with liver cirrhosis (Child–Pugh score ≥ 7, aged 48–79 years), 30 healthy young volunteers (aged 18–40 years), and 20 healthy elderly volunteers (aged 61–80 years) were enrolled. All participants received a single oral dose of 0.5 g phenacetin. Liquid chromatography tandem mass spectrometry was used to determine the serum concentrations of phenacetin and its metabolites, including acetaminophen, acetaminophen glucuronide and acetaminophen sulfate. RESULTS: The serum concentration of phenacetin was significantly higher in cirrhotic patients than those in either of the healthy volunteer groups ( P < 0.001). It was higher in healthy elderly volunteers than that in healthy young ones but there was no statistically significant difference ( P > 0.05) between them. The serum concentrations of acetaminophen, acetaminophen glucuronide and acetaminophen sulfate were significantly lower in cirrhotic patients than in the healthy controls ( P < 0.001). The serum concentrations of these three metabolites in healthy elderly volunteers were lower than those in healthy younger volunteers but again, there was no statistical significant difference ( P > 0.05). The serum concentration of acetaminophen in healthy male volunteers was significantly higher than that in the women ( P < 0.05). CONCLUSION: Monitoring cytochrome P450 1A2 (CYP450 1A2)‐mediated phenacetin metabolism is a simple and efficient method for evaluating human LRF. This method would warrant further validation in a large cohort clinical study.