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Possible enhancement of the first‐pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects
Author(s) -
Xiaofang Dong,
Z. Zhi Ping,
Xiaofeng Zhong,
Chong Shu,
Fattore,
Gatti,
D’Urso,
Emilio Perucca
Publication year - 1999
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1999.00065.x
Subject(s) - phenacetin , cyp1a2 , ingestion , chemistry , grapefruit juice , caffeine , metabolism , food science , pharmacology , pharmacokinetics , biochemistry , medicine , chromatography , cytochrome p450
Aims 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.