title: Biotransformation of the ipecac alkaloids cephaeline and emetine from ipecac syrup in rats.
abstract: 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 9-0-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 of 3H-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 of 3H-emetine was 6.9% of the dose. Emetine, cephaeline and 9-0-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.
authors: R&D Division, Tsumura & Co, Ltd, Inashiki, Ibaraki, Japan.
authors: Takayuki
authors: T
authors: Asano
authors: Junko
authors: J
authors: Watanabe
authors: Chiharu
authors: C
authors: Sadakane
authors: Kazuhisa
authors: K
authors: Ishihara
authors: Kazuhiro
authors: K
authors: Hirakura
authors: Yoko
authors: Y
authors: Wakui
authors: Toshihiko
authors: T
authors: Yanagisawa
authors: Masayuki
authors: M
authors: Kimura
authors: Hideo
authors: H
authors: Kamei
authors: Takemi
authors: T
authors: Yoshida
authors: Yuichi
authors: Y
authors: Fujii
authors: Mamoru
authors: M
authors: Yamashita
mesh_terms: D000818:Animals; D001345:Autoradiography; D001646:Bile / Q000737:chemistry; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003903:Deuterium; D004639:Emetics / Q000493:pharmacokinetics* / Q000652:urine; D004640:Emetine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000652:urine; D005243:Feces / Q000737:chemistry; D007486:Ipecac / Q000493:pharmacokinetics* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
chemical_list: D004639:Emetics; D014316:Tritium; D007486:Ipecac; D003903:Deuterium; C005963:cephaelin; D004640:Emetine