Abstract
The reductive metabolism in vivo of a flavoring additive,trans-4-phenyl-3-buten-2-one (PBO;trans-methyl styryl ketone) was investigated in rats and dogs. In both species, the double bond-reduced product, 4-phenyl-2-butanone (PBA), was detected by HPLC as the predominant species in blood after i.v. administration of PBO. PBA detected in rat blood was identified by comparison to the authentic sample. In contrast, the carbonyl-reduced product,trans-4-phenyl-3-buten-2-ol (PBOL) was also detected as a minor metabolite of PBO in both species. The area under the curve of PBOL in rat blood was only 3% of that of PBA. PBO was mutagenic in the Ames test using Salmonella typhimurium TA 100 when S-9 mix was added, but PBA and PBOL were not. It appears that PBO is mainly metabolized to PBA in vivo in rats and dogs as a detoxification pathway.
Footnotes
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Send reprint requests to: Dr. Shigeyuki Kitamura, Institute of Pharmaceutical Sciences, Hiroshima University, School of Medicine, 1–2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail:kitamura{at}pharm.hiroshima-u.ac.jp
- Abbreviations used are::
- PBO
- trans-4-phenyl-3-buten-2-one
- PBA
- 4-phenyl-2-butanone
- PBOL
- trans-4-phenyl-3-buten-2-ol
- AUC
- area under the curve
- GC
- gas chromatography
- Received March 9, 1999.
- Accepted April 12, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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