Hepatic and gastrointestinal first‐pass effects of vitexin‐4″‐O‐glucoside in rats. (30th July 2013)

• Record Type: Journal Article
• Authors: Chen, Yinghui; Zhang, Wenjie; Li, Di; Ai, Junjun; Meng, Yihan; Ying, Xixiang; Kang, Tingguo
• Is Part Of: Journal of pharmacy and pharmacology. Volume 65:Number 10(2013:Oct.)
• Page Start: 1500
• Page End: 1507
• Publication Date: 2013-07-30
• Subjects: bioavailability -- first‐pass effect -- HPLC -- vitexin‐4″‐O‐glucoside; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12121
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: 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.