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Genistein alters caffeine exposure in healthy female volunteers

  • Clinical Trial
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

This study investigated the effect of 1 g genistein daily for 14 days on caffeine-based metrics of cytochrome P4501A2 (CYP1A2), cytochrome P4502A6 (CYP2A6), N-acetyltransferase 2 (NAT2), and xanthine oxidase (XO).

Methods

A single dose of 100 mg caffeine was administered once before and once on the last day of a 14-day treatment regime with 1 g genistein once daily to 18 healthy female volunteers. Urine and blood samples were collected up to 12 and 24 h, respectively, after each caffeine dose. Using high-performance liquid chromatography (HPLC), caffeine and 1,7-dimethylxanthine (17X) were quantified in plasma, whereas 17X, 1,7-dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U), and 5-acetylamino-6-formylamine-3-methyluracil (AFMU) were quantified in urine. Urinary metabolite ratios were calculated to assess enzyme activities and compared between administrations using analysis of variance (ANOVA).

Results

Genistein decreased the urinary caffeine metabolite ratio used to assess CYP1A2 activity by 41% [90% confidence interval (CI) 28–51%). The urinary ratio indicating XO activity decreased by 29% (90% CI 24–32%), whereas urinary ratio for CYP2A6 activity increased by 47% (90% CI 29–66%) after 2 weeks of genistein. The NAT2 urinary caffeine metabolite ratio did not change significantly.

Conclusions

Two weeks of intake of 1 g genistein daily led to decreases in CYP1A2 and XO activity and an increase in CYP2A6 activity, whereas NAT2 activity did not change in healthy Chinese female volunteers. Pharmacokinetics of other substrates of the enzymes investigated here may be influenced in a similar manner.

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Abbreviations

CYP450:

CYP450 monooxygenase system

CYP1A2:

cytochrome P4501A2

CYP2A6:

cytochrome P4502A6

NAT2:

N-acetyltransferase 2

XO:

xanthine oxidase

17X:

1,7-dimethylxanthine

17U:

1,7-dimethylurate

1X:

1-methylxanthine

1U:

1-methylurate

AFMU:

5-acetylamino-6-formylamino-3-methyluracil

UCMR:

urinary caffeine metabolite ratio

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Authors and Affiliations

  1. Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Xiang-Ya School of Medicine, 110 Xiang-Ya road, Changsha, Hunan, 410078, People’s Republic of China

    Yao Chen, Chang-Qiong Xiao, Yi-Jing He, Bi-Lian Chen, Guo Wang, Gan Zhou, Wei Zhang, Zhi-Rong Tan, Shan Cao, Li-Ping Wang & Hong-Hao Zhou

Authors
  1. Yao Chen
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  2. Chang-Qiong Xiao
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  3. Yi-Jing He
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  4. Bi-Lian Chen
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  5. Guo Wang
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  6. Gan Zhou
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  7. Wei Zhang
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  8. Zhi-Rong Tan
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  9. Shan Cao
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  10. Li-Ping Wang
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  11. Hong-Hao Zhou
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Corresponding author

Correspondence to Hong-Hao Zhou.

Additional information

This work was supported by the National Scientific Foundation of China (grant # 30801421) Huge Project to Boost Chinese Drug Development (grant # 2009ZX09501-032), 863 Projects (No. 2009AA022710, 2009AA022703, 2009AA022704) Fund by State Key Laboratory of Drug Research (grant # SIMM0812KF-01) and Research Fund for the Young Teachers Boost Plans of Chinese Central College (grant #201012200047).

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Chen, Y., Xiao, CQ., He, YJ. et al. Genistein alters caffeine exposure in healthy female volunteers. Eur J Clin Pharmacol 67, 347–353 (2011). https://doi.org/10.1007/s00228-010-0964-5

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  • DOI: https://doi.org/10.1007/s00228-010-0964-5

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