Pharmacokinetics of ferulic acid and potential interactions with Honghua and clopidogrel in rats

Abstract

Ferulic acid (FA), a compound isolated from herbs, has a big potential to be developed into a useful drug for the treatment of cardiovascular disease. Early estimation of potential drug interaction is critical for drug development. As a common Chinese herb and Western drug respectively, Honghua and clopidogrel are often combined with FA-containing herbs to treat cardiovascular disease in clinical practice. This study aimed to investigate the pharmacokinetics of FA and potential interaction with Honghua and clopidogrel in rats. The experiments were performed on following three groups: FA alone (10mg/kg, P.O.), combination of FA and Honghua (700 mg/kg, P.O.), combination of FA and clopidogrel (7 mg/kg, P.O.). Blood samples were collected before dosing and at 0, 2, 4, 7, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180 and 210 min after drug administration to determine the plasma drug concentration of FA. FA was rapidly absorbed following oral administration with a mean time to peak plasma concentration (T(max)) of 0.03 h. The corresponding maximum plasma concentration (C(max)) and the area under the concentration-time curve (AUC) were 8174.55 ng/L and 2594.45 h ng/mL respectively. Coadministration of Honghua and clopidogrel resulted in a 63.5% and 79.7% increase in the AUC respectively. The C(max) of FA was significantly increased by coadministration with clopidogrel (74.3%, p<0.01). Moreover, the T(max) of FA when coadministered with Honghua or clopidogrel was 3 and 3.76 times slower than when administered alone. Other pharmacokinetic parameters estimated for FA were also altered by the coadministrations, but no statistically significant differences were observed. FA was rapidly absorbed with a low bioavailability after a single oral administration. The pharmacokinetics profile of FA in rats was partly altered by the coadministration of FA with Honghua or clopidogrel.