Zhang Ruhong, Jie Jinjie, Zhou Yan'an, Cao Zhijian, Li Wenxin
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, P. R. China.
Am J Chin Med. 2009;37(4):657-67. doi: 10.1142/S0192415X09007144.
This study was designed to explore the pharmacokinetic interaction of Panax ginseng with fexofenadine in rats. Sprague-Dawley (SD) male rats were divided randomly into four groups: control oral and treatment oral dose groups (n = 6, respectively); control intravenous and treatment intravenous dose groups (n = 5, respectively). A single dose of fexofenadine (10 mg/kg for intravenous group rats and 100 mg/kg for oral dose group rats) was administered after 14 consecutive days of gastric gavage feeding of panax ginseng suspension (150 mg/kg/day) to treatment groups while the same volume of vehicle (1.6% ethanol) was administered as placebo to control groups. Blood samples were collected from 0 to 12 hours and levels of fexofenadine were measured by LC-MS/MS. Tissues were harvested to determine tissue/blood ratios. The pharmacokinetic parameters of fexofenadine were calculated using non-compartmental analysis. In the oral dose groups, (extravenous) panax ginseng decreased the area under the curve between 0-12 hours (AUC(0-12)) from 102490.7 +/- 25273.5 to 49933.3 +/- 12072.9 min*ng/ml (p < 0.005), decreased Cmax from 1102.0 +/- 116.6 to 274.3 +/- 180.6 ng/ml (p < 0.001), and significantly decreased ratios of brain to plasma concentration (B/P) (p < 0.05). In the intravenous groups, panax ginseng only reduced B/P ratios (p < 0.05). The mean bioavailability (F(ev)) of fexofenadine was decreased by 16.1% in the extravenous dose treatment group (p < 0.05). Long term administration of panax ginseng to rats might induce both intestinal and brain endothelium p-glycoprotein (p-gp) expression. In addition, long term use of panax ginseng reduced the bioavailability of concurrently administered fexofenadine.
本研究旨在探讨人参对大鼠体内非索非那定药代动力学的影响。将雄性Sprague-Dawley（SD）大鼠随机分为四组：口服对照组和口服给药治疗组（每组n = 6）；静脉注射对照组和静脉注射给药治疗组（每组n = 5）。在治疗组连续14天胃管饲人参悬浮液（150mg/kg/天）后，给予单剂量非索非那定（静脉注射组大鼠为10mg/kg，口服给药组大鼠为100mg/kg），而对照组给予相同体积的溶媒（1.6%乙醇）作为安慰剂。在0至12小时采集血样，采用液相色谱-串联质谱法（LC-MS/MS）测定非索非那定水平。采集组织以测定组织/血液比值。采用非房室分析计算非索非那定的药代动力学参数。在口服给药组中，人参使0至12小时曲线下面积（AUC(0-12)）从102490.7±25273.5降至49933.3±12072.9min*ng/ml（p < 0.005），使Cmax从1102.0±116.6降至274.3±180.6ng/ml（p < 0.001），并显著降低脑/血浆浓度比值（B/P）（p < 0.05）。在静脉注射组中，人参仅降低B/P比值（p < 0.05）。非索非那定的平均生物利用度（F(ev)）在静脉注射给药治疗组中降低了16.1%（p < 0.05）。长期给大鼠服用人参可能会诱导肠道和脑内皮细胞P-糖蛋白（P-gp）表达。此外，长期使用人参会降低同时服用的非索非那定的生物利用度。
