title: Hepatic, gastric and intestinal first-pass effects of vitexin-2''-O-rhamnoside in rats by ultra-high-performance liquid chromatography.
abstract: Previous research in our laboratory found that the absolute bioavailability of vitexin-2''-O-rhamnoside (VR) was quite low at 4.89%. A rapid and sensitive UHPLC method using hesperidin as an internal standard was therefore developed and validated to investigate the reasons for this by determining VR in rat plasma after administering intravenously, intraportally (5 mg/kg), intraduodenally and intragastrically (40 mg/kg) to the rat model of the hepatic, gastric and intestinal first-pass effects. As only a high intestinal first-pass effect of VR was found, that is, there existed a low bioavailability of VR (2.40%), inhibitors of P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A), including verapamil, cyclosporin A and midazolam, and absorption enhancers, including bile salts and borneol, combined with VR, were instilled into duodenum to evaluate the effects on bioavailability of VR. The results demonstrated that area under the concentration-time curve (AUC) values of VR slightly increased after administration of verapamil, cyclosporin A and midazolam, indicating that CYP3A and P-gp do not play an important role in the first-pass effect in the intestine. AUC values of VR significantly increased after administering bile salts or borneol, indicating that the low bioavailability of VR was mainly related to its poor absorption in the intestine.
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, China.
authors.forename: Yucong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Du
authors.affiliation: First Clinical School, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, China.
authors.forename: Zheming
authors.initials: Z
authors.lastname: Ying
authors.affiliation: First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
authors.forename: Aijing
authors.initials: A
authors.lastname: Leng
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, China.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, China.
authors.forename: Cuiyu
authors.initials: C
authors.lastname: Li
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, China.
authors.forename: Xixiang
authors.initials: X
authors.lastname: Ying
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, China.
authors.forename: Tingguo
authors.initials: T
authors.lastname: Kang
mesh_terms: D000818:Animals; D047310:Apigenin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004386:Duodenum / Q000098:blood supply / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013270:Stomach / Q000098:blood supply
chemical_list: C021329:vitexin rhamnoside; D047310:Apigenin
keywords: bioavailability; first-pass effect; vitexin-2”-O-rhamnoside