In vivo inhibitory effects of puerarin on selected rat cytochrome P450 isoenzymes.

Puerarin, the major bioactive constituent in kudzu root, is used widely in China for the treatment of cardiovascular diseases and diabetes. The purpose of this study was to find out whether puerarin influences the effect on rat cytochrome P450 (CYP) enzymes (CYP2B6, CYP2C9 and CYP3A4) by using cocktail probe drugs in vivo. A cocktail solution at a dose of 5 mL/kg, which contained bupropion (20 mg/kg), tolbutamide (5 mg/kg) and midazolam (20 mg/kg), was given as oral administration to rats treated with 10 days oral administration of puerarin. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The results showed that treatment with multiple doses of puerarin had inhibitory effects on rat CYP2B6, CYP2C9 and CYP3A4 enzyme activities. Therefore, caution is needed when puerarin is co-administered with CYP substrates, in view of herb-drug interactions.