title: Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects.
abstract: OBJECTIVE
  This serendipitous study revealed an unexpected effect of Jufeng grape juice on the CYP1A2-mediated metabolism of phenacetin. Investigation of the inhibition of CYP1A2 by grapefruit juice was involved but a translation error led to the grape juice substitution.
  
  
  METHODS
  Twelve healthy subjects took a single oral dose of phenacetin (900 mg) on two randomized occasions together with 200 ml water or grape juice. Plasma phenacetin and paracetamol concentrations were assessed by h.p.l.c.
  
  
  RESULTS
  Ingestion of grape juice was associated with reduced plasma phenacetin concentrations, while paracetamol levels were unaffected. Paracetamol to phenacetin AUC ratios increased from 13.9+/-3.1 to 24.3+/-3.8 after ingestion of grape juice.
  
  
  CONCLUSIONS
  These findings suggest enhanced first-pass metabolism of phenacetin, due to CYP1A2 activation by grape juice or to desaturation of CYP1A2 isoenzymes secondary to a slower rate of phenacetin absorption.
authors.affiliation: Institute of Clinical Pharmacology, Great Chinese Wall Hospital, Beijing, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Xiao Dong
authors.forename: Z
authors.initials: Z
authors.lastname: Zhi Ping
authors.forename: W
authors.initials: W
authors.lastname: Zhong Xiao
authors.forename: C
authors.initials: C
authors.lastname: Chong Shu
authors.forename: C
authors.initials: C
authors.lastname: Fattore
authors.forename: G
authors.initials: G
authors.lastname: Gatti
authors.forename: S
authors.initials: S
authors.lastname: D'urso
authors.forename: E
authors.initials: E
authors.lastname: Perucca
mesh_terms: D000082:Acetaminophen / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002681:China; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007527:Isoenzymes; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010615:Phenacetin / Q000097:blood / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000494:pharmacology*; D011897:Random Allocation; D019685:Rosales / Q000737:chemistry*; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010936:Plant Extracts; D000082:Acetaminophen; D019388:Cytochrome P-450 CYP1A2; D010615:Phenacetin