Objectives: Ciclosporin and sirolimus, two immunosuppressive agents with narrow therapeutic windows, are mainly metabolized by Cytochrome 3A4 (CYP3A4). A clinical case of toxic blood levels of these drugs after the consumption of a '24-flavours' tea was reported. This study aims to identify the causative ingredients of the 24-flavour herbal tea in the inhibition of CYP3A4 metabolism.
Methods: Two commercially available 24-flavour tea products purchased in Hong Kong and the six plant constituents were tested for their CYP3A4 inhibitory effects utilizing an in-vitro fluorometric assay.
Key findings: Of the commercially available teas available in Hong Kong, the most potent inhibitory effect was observed with the tea consumed in the initial clinical case. Of the six universal constituents, chrysanthemum exhibited the greatest inhibitory effect, with an IC50 of 95.7 μg/ml. Dandelion, liquorice and bishop's weed have IC50 of 140.6, 148.4 and 185.5 μg/ml, respectively. Field mint and Japanese honeysuckle have weaker inhibitory effect on CYP3A4 with IC50 of 1153.3 and 1466.3 μg/ml.
Conclusions: This study confirms the possible implication of herbal tea constituents in the inhibition of ciclosporin and sirolimus' CYP3A4 metabolism. Combined usage of herbal teas with drug should be closely monitored.
Keywords: Cytochrome 3A4; ciclosporin; herb-drug interaction; herbal teas; sirolimus; traditional Chinese medicine.
© 2014 Royal Pharmaceutical Society.