The Effect Of Daidzein On CYP3A Enzyme, And The Potential Drug Interaction With Simvastatin In Vivo

Aim: To investigate the effect of daidzein on CYP3A enzyme activity, and the possible drug interaction with simvastatin in healthy volunteers.Methods: 12 healthy male volunteers were recruited in this two-phase, randomized, crossover clinical trial. All subjects took 200mg daizdzein tablets two times daily or placebo for consecutive 6 days according to the different phase. On the seventh day of each phase, the venous blood sample from 0-24 hour were collected after a combination of 40mg simvastatin and 7.5mg midazolam were given to every volunteer. The activity of CYP3A was reflected by the pharmacokinetics of midazolam.Results: The CYP3A enzyme was significantly inhibited after the administration of daidzein, the AUC(0-24), AUC(0-8) and Cmax were increased by 20.66ï¼…, 95ï¼…CI(2.62ï¼…, 38.76ï¼…, P=.024), 19.95ï¼…, 95ï¼…CI(-0.23ï¼…, 39.84ï¼…, P=.042) and 27.35ï¼…, 95ï¼…CI(-4.25ï¼…, 54.71ï¼…, P=.043), respectively. However, no significant discrepancy was detected in the pharmacokinetics parameters of simvastatin and its main metabolite simvastatin aicd.Conclusion: High dose of daidzein tablets may inhibit the activity of CYP3A in vivo, which needs the awareness of physicians because of the potential drug interaction. However, the suppression had no effect on the pharmacokinetics parameters of simvastatin.