Hepatic and gastrointestinal first-pass effects of vitexin-4″-O-glucoside in rats.

OBJECTIVES

This paper was to clarify the reasons of low bioavailability of vitexin-4″-O-glucoside (VOG) in rats via hepatic combined with gastrointestinal first-pass effect.

METHODS

Observed the hepatic first-pass effect through the comparison of area under the plasma concentration-time curve from zero to infinity (AUC0→∞ ) of VOG in arterial plasma after femoral and portal vein administration (10 mg/kg), similarly, evaluated the gastrointestinal first-pass effect after portal vein (10 mg/kg) and gastrointestinal administration (20 mg/kg). For the study on regulatory mechanisms of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) on the bioavailability of VOG, the solution of verapamil hydrochloride (60 mg/kg) was instilled into intestine at 10 min before the infusion of VOG.

KEY FINDINGS

The bioavailability of VOG after intraportal, intestinal as well as gastric administration was 45.1%, 8.1% and 9.8%, respectively. The value of AUC0→∞ for verapamil group was approximately 1.4-fold higher than that for normal saline group, meaning that perhaps CYP3A participated in the metabolism of VOG or P-gp transported VOG outside.

CONCLUSIONS

The hepatic and intestinal first-pass effect were considered to mostly contribute to the low bioavailability of VOG in rats, and the gastric first-pass effect should be neglected. Also, the contribution of CYP3A to metabolism and P-gp mediated efflux have played a significant role in low bioavailability of VOG.