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In vitro evidence for bakuchiol's influence towards drug metabolism through inhibition of UDP-glucuronosyltransferase (UGT) 2B7.

BACKGROUND
Inhibition of drug-metabolizing enzymes (DMEs) has been regarded as one of the most important reason for clinical drug-drug interaction.


AIM
The aim of the present study is to evaluate the inhibition of bakuchiol towards UDP-glucuronosyltransferase (UGT) 2B isoforms.


METHODS
In vitro recombinant UGT2B-catalyzed 4-methylumbelliferone glucuronidation was used as the probe reaction. Dixon plot and Lineweaver-Burk plot were employed to determine the inhibition kinetic type, and nonlinear regression of data was utilized to calculate the inhibition kinetic parameter (Ki). In vitro-in vivo extrapolation (IVIVE) was carried out to predict in vivo inhibition magnitude.


RESULTS
Among the tested UGT2B isoforms, UGT2B7 was inhibited by the strongest intensity. The noncompetitive inhibition was demonstrated by the results obtained from Dixon plot and Lineweaver-Burk plot. The Ki value was calculated to be 10.7 µM. In combination with the reported concentration after an intravenous administration of bakuchiol (15 mg/kg) in rats, the high risk of in vivo inhibition of bakuchiol towards UGT2B7-catalyzed metabolism of drugs was indicated.


CONCLUSION
All these results provide an important information for the risk evaluation of the clinical utilization of bakuchiol.