title: Hepatic and gastrointestinal first-pass effects of vitexin-4″-O-glucoside in rats.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, China.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Chen
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.forename: Junjun
authors.initials: J
authors.lastname: Ai
authors.forename: Yihan
authors.initials: Y
authors.lastname: Meng
authors.forename: Xixiang
authors.initials: X
authors.lastname: Ying
authors.forename: Tingguo
authors.initials: T
authors.lastname: Kang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D027825:Crataegus / Q000737:chemistry; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000201:enzymology / Q000378:metabolism*; D005960:Glucosides / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007529:Isoflavones / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D057230:Limit of Detection; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008516:Medicine, Chinese Traditional; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005960:Glucosides; D007529:Isoflavones; C477953:isovitexin-4'-O-glucoside; D051544:Cytochrome P-450 CYP3A
keywords: HPLC; bioavailability; first-pass effect; vitexin-4″-O-glucoside