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Biotransformation of the ipecac alkaloids cephaeline and emetine from ipecac syrup in rats

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Summary

The metabolism of cephaeline and emetine, which are the primary active components of ipecac syrup, were investigated in rats. Cephaeline-6′-O-glucuronide was found to be a biliary metabolite of cephaeline. Cephaeline (6′-O-demethylemetine) and 9-O-demethylemetine were observed to be enzyme-hydrolyzed biliary metabolites of emetine. Cephaeline was conjugated to glucuronide, while emetine was demethylated to cephaeline and 9-O-demethylemetine, and may be conjugated to glucuronides afterwards. Urine, feces and bile were collected from rats within 48 hours following the administration of ipecac syrup containing tritium (3H)-labeled cephaeline or emetine. Metabolites were separated and quantified by thin layer chromatography (TLC) or high-performance liquid chromatography (HPLC). Biliary and urinary excretion rates of3H-cephaeline were 57.5% and 16.5% of the dose, respectively. Cephaeline-6′-O-glucuronide was comprised 79.5% of biliary radioactivity and 84.3% of urinary radioactivity. Unchanged cephaeline was detected in 42.4% of the dose in feces. Biliary excretion rate of3H-emetine was 6.9% of the dose. Emetine, cephaeline and 9-O-demethylemetine comprised 5.8%, 43.2% and 13.6% in hydrolyzed bile, respectively. There were no emetine-derived metabolites in urine or feces. The occurrence of unchanged emetine was 6.8% and 19.7% of the dose in urine and feces, respectively.

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Authors and Affiliations

  1. New Drug Discovery Laboratories, R&D Division, Tsumura & Co., Ltd., 3586 Yoshiwara, Ami-machi, 300-1192, Inashiki, Ibaraki, Japan

    Takayuki Asano

  2. Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Shinagawaku, Tokyo, Japan

    Takemi Yoshida

  3. Department of Emergency Medicine, University of Tsukuba School of Medicine, Tsukuba, Japan

    Mamoru Yamashita

Authors
  1. Takayuki Asano
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  2. Junko Watanabe
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  3. Chiharu Sadakane
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  4. Kazuhisa Ishihara
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  5. Kazuhiro Hirakura
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  6. Yoko Wakui
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  7. Toshihiko Yanagisawa
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  8. Masayuki Kimura
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  9. Hideo Kamei
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  10. Takemi Yoshida
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  11. Yuichi Fujii
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  12. Mamoru Yamashita
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Asano, T., Watanabe, J., Sadakane, C. et al. Biotransformation of the ipecac alkaloids cephaeline and emetine from ipecac syrup in rats. Eur. J. Drug Metab. Pharmacokinet. 27, 29–35 (2002). https://doi.org/10.1007/BF03190402

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  • DOI: https://doi.org/10.1007/BF03190402

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