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Caffeic acid as well as its oxidation products exert a spectrum of biological effects in in vitro testing. To get an idea of the amount as well as the mode of biotransformation, caffeic acid metabolism was investigated by means of the isolated perfused rat liver. The first-pass effect was not pronounced: 93.3% of caffeic acid dose appeared unchanged after one liver passage. Products of caffeic acid oxidation (cyclolignan derivatives) as well as ferulic and isoferulic acid as methylation products were found in the perfusion medium. In addition, a cyclization product, esculetin, was observed. In the bile, mainly glucuronides as well as sulfates of caffeic acid could be determined. Thus, oxidation products and other metabolites formed by liver metabolism can be responsible for the biological effects in vivo.
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