Effects of Ferulic Acid on the Pharmacokinetics of Intragastrically Administered Losartan in Rats

OBJECTIVE To study the influence of ferulic acid on the pharmacokinetics of losartan and E-3174 in rats. METHODS Twelve rats (six for each group) were administered orally with 50 mg·kg^-1 ferulic acid (experimental group) or 0.5% CMC-Na (control group) every day for 7 d. On the eighth day, losartan (5 mg·kg^-1) was given to all rats orally 30 min after taking ferulic acid or CMC-Na. Blood samples were collected from the tail vein before giving losartan and at the time points of 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 h after administration. The plasma concentrations of losartan and E-3174 were determined by UPLC-MS/MS. RESULTS There was no significant difference on the pharmacokinetic parameters of losartan between the control group and the experimental group. However, the pharmacokinetic parameters of E-3174 in the experimental group, such as AUC_(0-t), AUC_(0-∞), C_max were significantly rose (P<0.05) while CL/F and T_max were significantly decreased (P<0.05) compared with the control group. CONCLUSION This study indicates that the pharmacokinetics of E-3174 in rats can be greatly changed by ferulic acid, slow down the metabolism and increase the concentration. However, ferulicacid has no effect on that of losartan.