Study on the First-Pass Effects of Vitexin-4′-O-Glucoside in Rats in vivo / 中国药房

ABSTRACT

OBJECTIVE:To investigate the first-pass effect and mechanism of vitexin-4′-O-glucoside(VG)in rats so as to pro-vide a basis for new drug development. METHODS:10 SD rats were divided into a group of hepatic portal venous administration and a group of femoral venous administration,which respectively received VG iv at superior mesenteric vein and femoral vein,and then metabolic rate was calculated by finding out the AUC of VG in the rats’livers. 15 SD rats were divided into a group of gastric infusion,a group of intestinal infusion and a group of hepatic portal venous infusion,which respectively received VG by infusion at gastric fundus and duodenum and iv at superior mesenteric vein,and then metabolic rate was calculated by finding out the AUC of VG in the rats’stomachs and intestines. 15 SD rats were divided into a group of intestinal infusion,a group of femoral venous administration and a group of normal saline. At 10 min before administration,the former two groups were given by infusion vera-pamil injection(60 ml/kg),the substrate of CYP3A and P-glycoprotein(P-gp);and the group of normal saline were given by infu-sion of isometric normal saline,and then the rats were given VG as above to observe the effect of verapamil on intestinal absorp-tion of VG. RESULTS:The metabolic rates of VG in the liver,stomach and intestine were 54.9%,1.7% and 91.9% respectively. After infusion of verapamil,slight increase in AUC of VG was found in the rats in the group of intestinal infusion. CONCLU-SIONSThe first-pass effects in the liver and intestine are the main factors related to the low bioavailability of VG. Based on pre-liminary judgment,VG is the substrate of intestinal CYP3A and/or P-gp.