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Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer

Prostate Cancer and Prostatic Diseases volume 5, pages 128–131 (2002)Cite this article

Abstract

The caffeine test measures the activity of cytochrome P450 (CYP1A2) which is a major enzyme involved in the activation of flutamide. The usefulness of this test in predicting flutamide-induced hepatic injury in patients with prostate cancer was examined. The subjects were: (1) five patients whose aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level rose to 100 IU/l or higher following the start of flutamide (moderately injured group); (2) four patients whose AST and ALT levels were higher than normal but less than 100 IU/l (mildly injured group); and (3) two patients whose hepatic function remained normal (normal group). The subjects were each given canned coffee to drink. Urinary caffeine (137X), paraxanthine (17X) and 1, 7-dimethyluric acid (17U) levels were measured 4–5 h later. The metabolite ratio, (17U+17X)/137X, was calculated to serve as an indicator of CYP1A2 activity. The metabolite ratio for the moderately injured group (3.98±1.56) and the mildly injured group (5.55±1.42) were lower than that for the normal group (9.56). The results suggest that a decrease in CYP1A2 activity is involved in the onset of flutamide-induced hepatic injury, and that the caffeine test seems to provide a useful means of its prediction.

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References

  1. Aso Y et al. Clinical evaluation of flutamide, a pure antiandrogen, in prostatic cancer phase II dose-finding study Acta Urol Jpn 1993 39: 391–403

    CAS  Google Scholar 

  2. Satoh T et al. A case of fulminant hepatitis caused by antiandrogen, flutamide in a patient with prostate cancer Nippon Hinyokika Gakkaishi 1997 88: 694–696

    CAS  Google Scholar 

  3. Sakurai M et al. A case of flutamide-induced acute cholestatic hepatitis Rinsho Hinyokika 1998 52: 851–853

    Google Scholar 

  4. Okaneya T, Murata Y, Kinebuchi Y . Fatal hepatic failure following hepatitis caused by flutamide: a case report Nippon Hinyokika Gakkaishi 1999 90: 590–593

    CAS  Google Scholar 

  5. Fau D et al. Toxicity of the antiandrogen flutamide in isolated rat hepatocytes J Pharmacol Exp Ther 1994 269: 954–962

    CAS  PubMed  Google Scholar 

  6. Berson A et al. Metabolic activation of the nitroaromatic antiandrogen flutamide by rat and human cytochromes P-450, including forms belonging to the 3A and 1A subfamilies J Pharmacol Exp Ther 1993 265: 366–372

    CAS  PubMed  Google Scholar 

  7. Watanabe N et al. In vitro effects of fluoroquinolone anti-bacterial agents on flutamide metabolism in human liver microsomes Jpn J Clin Pharmacol Ther 2001 32: 65–71

    Article  CAS  Google Scholar 

  8. Brockmöller J, Roots I . Assessment of liver metabolic function. Clinical implications Clin Pharmacokinet 1994 27: 216–248

    Article  Google Scholar 

  9. Daniel SS, Bertino JS Jr, Nafziger AN . Phenotyping of drug-metabolizing enzymes in adults: a review of in vivo cytochrome P450 phenotyping probes Pharmacogenetics 2000 10: 187–216

    Article  Google Scholar 

  10. Nakajima M et al. Phenotyping of CYP1A2 in Japanese population by analysis of caffeine urinary metabolites: absence of mutation prescribing the phenotype in the CYP1A2 gene Cancer Epidemiol Biomarkers Prevention 1994 3: 413–421

    CAS  Google Scholar 

  11. Butler MA et al. Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites Pharmacogenetics 1992 2: 116–127

    Article  CAS  Google Scholar 

  12. Carrillo JA, Benítez J . Caffeine metabolism in a healthy Spanish population: N-acetylator phenotype and oxidation pathways Clin Pharmacol Ther 1994 55: 293–304

    Article  CAS  Google Scholar 

  13. Kagebayashi Y et al. Total androgen blockade for prostate cancer Acta Urol Jpn 1997 43: 197–201

    CAS  Google Scholar 

  14. Ozono S et al. A prospective randomized multicenter study of chlormadinone acetate versus flutamide in total androgen blockade for prostate cancer Jpn J Clin Oncol 2000 30: 389–396

    Article  CAS  Google Scholar 

  15. Yamaguchi A et al. Study of flutamide-induced liver disorders Nishinihon J Urol 2001 63: 469–471

    Google Scholar 

  16. Nakagawa Y, Koyama M, Matsumoto M . Flutamide-induced hepatic disorder and serum concentrations of flutamide and its metabolites in patients with prostate cancer Acta Urol Jpn 1999 45: 821–826

    CAS  Google Scholar 

  17. Wada T et al. Risk factor of liver disorders caused by flutamide—statistical analysis using multivariate logistic regression analysis Acta Urol Jpn 1999 45: 521–526

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, Nara Medical University, Nara, Japan

    S Ozono, A Yamaguchi, H Mochizuki, T Kawakami, K Fujimoto, T Otani, K Yoshida & Y Hirao

  2. Nippon Kayaku Co. Ltd., Tokyo, Japan

    M Ichinei & T Yamashita

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  1. S Ozono
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  2. A Yamaguchi
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  3. H Mochizuki
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  4. T Kawakami
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  7. K Yoshida
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  8. M Ichinei
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  9. T Yamashita
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Correspondence to S Ozono.

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Ozono, S., Yamaguchi, A., Mochizuki, H. et al. Caffeine test in predicting flutamide-induced hepatic injury in patients with prostate cancer. Prostate Cancer Prostatic Dis 5, 128–131 (2002). https://doi.org/10.1038/sj.pcan.4500564

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  • DOI: https://doi.org/10.1038/sj.pcan.4500564

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