title: Evaluating human liver reserve function by measuring serum concentrations of phenacetin and its metabolites.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, Central Hospital of Xuhui District, Shanghai, China. ncxwj@126.com
authors.forename: Wen Jian
authors.initials: WJ
authors.lastname: Xiong
authors.forename: Hui
authors.initials: H
authors.lastname: Jin
authors.forename: Shui Jun
authors.initials: SJ
authors.lastname: Li
authors.forename: Jia Chen
authors.initials: JC
authors.lastname: Jin
authors.forename: Bei Na
authors.initials: BN
authors.lastname: Ji
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000502:physiology*; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000378:metabolism; D008111:Liver Function Tests / Q000009:adverse effects / Q000379:methods*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010615:Phenacetin / Q000097:blood / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012737:Sex Factors; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D010615:Phenacetin