title: Hepatic, gastric, and intestinal first-pass effects of vitexin in rats.
abstract: BACKGROUND
  Recent research has demonstrated that vitexin exhibits a prominent first-pass effect. In this light, it is necessary to investigate the causes of this distinct first-pass effect.
  
  
  OBJECTIVE
  The aim of this study was to evaluate hepatic, gastric, and intestinal first-pass effects of vitexin in rats and, furthermore, to investigate the role of P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A) in the absorption and secretion of vitexin in the duodenum.
  
  
  METHODS
  Vitexin was infused into rats intravenously, intraportally, intraduodenally, and intragastrically (30 mg/kg). In addition, verapamil (50 mg/kg), a common substrate/inhibitor of P-gp and CYP3A, was also instilled with vitexin into the duodenum to investigate the regulatory action of P-gp and CYP3A. The plasma concentrations of vitexin were measured by the HPLC method using hesperidin as an internal standard.
  
  
  RESULTS
  The hepatic, gastric, and intestinal first-pass effects of vitexin in rats were 5.2%, 31.3%, and 94.1%, respectively. In addition, the total area under the plasma concentration-time curve from zero to infinity (AUC) of the vitexin plus verapamil group and of the normal saline group was 44.9 and 39.8 μgċ min/mL, respectively.
  
  
  CONCLUSIONS
  The intestinal first-pass effect of vitexin was considerable, and gastric and hepatic first-pass effects also contribute to the low absolute oral bioavailability of vitexin. The AUC of the vitexin plus verapamil group was slightly higher than that of the vitexin plus normal saline group (by approximately 1.13-fold), suggesting that verapamil does not play an important role in the absorption and secretion of vitexin.
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine , Dalian , China and.
authors.forename: He-Fei
authors.initials: HF
authors.lastname: Xue
authors.forename: Zhe-Ming
authors.initials: ZM
authors.lastname: Ying
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Meng
authors.forename: Xi-Xiang
authors.initials: XX
authors.lastname: Ying
authors.forename: Ting-Guo
authors.initials: TG
authors.lastname: Kang
mesh_terms: D000818:Animals; D047310:Apigenin / Q000378:metabolism* / Q000494:pharmacology; D027825:Crataegus; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010936:Plant Extracts / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D018515:Plant Leaves; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects
chemical_list: D010936:Plant Extracts; D047310:Apigenin; C032731:vitexin
keywords: HPLC; pharmacokinetics; verapamil