Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects

S. Xiao Dong, Z. Zhi Ping, W. Zhong Xiao, C. Chong Shu, C. Fattore, G. Gatti, S. D'Urso, E. Perucca

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)638-640
Number of pages3
JournalBritish Journal of Clinical Pharmacology
Volume48
Issue number4
DOIs
Publication statusPublished - 1999

Fingerprint

Phenacetin
Vitis
Eating
Cytochrome P-450 CYP1A2
Acetaminophen
Citrus paradisi
Isoenzymes
Area Under Curve
Healthy Volunteers
Water

Keywords

  • Cytochrome CYP1A2
  • Drug metabolism
  • Grape juice
  • Paracetamol
  • Phenacetin

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects. / Xiao Dong, S.; Zhi Ping, Z.; Zhong Xiao, W.; Chong Shu, C.; Fattore, C.; Gatti, G.; D'Urso, S.; Perucca, E.

In: British Journal of Clinical Pharmacology, Vol. 48, No. 4, 1999, p. 638-640.

Research output: Contribution to journalArticle

Xiao Dong, S. ; Zhi Ping, Z. ; Zhong Xiao, W. ; Chong Shu, C. ; Fattore, C. ; Gatti, G. ; D'Urso, S. ; Perucca, E. / Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects. In: British Journal of Clinical Pharmacology. 1999 ; Vol. 48, No. 4. pp. 638-640.
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AU - Zhi Ping, Z.

AU - Zhong Xiao, W.

AU - Chong Shu, C.

AU - Fattore, C.

AU - Gatti, G.

AU - D'Urso, S.

AU - Perucca, E.

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N2 - 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.

AB - 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.

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