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

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-SIONS:The 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.

Severe drowsiness caused by oral administration of low dose opioid in a patient with portal stenosis

<b>Purpose</b>: We report a case with portal vein stenosis that showed unexpected drowsiness induced by oral administration of low dose opioid, suggesting elevation of opioid level in blood. <b>Case report</b>: A 60-year-old woman developed portal vein stenosis caused by postoperative local recurrence and lymph node metastasis after operation of lower bile duct carcinoma. Her doctor administrated 10mg/day of oral controlled-release oxycodone tablet to her and she became drowsy. Therefore, we started powdered form of oral sustained release morphine with 10mg/day and reduced the dose to 5 mg/day; however, her drowsiness persisted. Finally, the symptom was remarkably improved when the administration was changed to a transdermal fentanyl patch (12.5μg/h). <b>Conclusion</b>: Adequate observation is required for cases with reduction in portal blood flow at the time of oral opioid administration. Because oral opioid can escape from first pass effect of the liver and opioid level in blood will be increasing. Furthermore, it is suggested that change in administration method from oral route to percutaneous one may be effective for improvement of adverse effects involving increased opioid-level in blood. Palliat Care Res 2008; 3(2): 331-334