黑顺片与大黄联用对次乌头碱在大鼠体内药动学的影响

Effects of Heishun Tablets Combined with Rheum palmatum on the Pharmacokinetics of Hypaconitine in Rats

目的：研究黑顺片与大黄联用对次乌头碱在大鼠体内药动学的影响。方法：取大鼠随机分为单用（黑顺片单煎液）组和联用（黑顺片-大黄合煎液）组，每组18只，ig相应药物，给药剂量均按黑顺片计为10 g（生药）/kg。分别于给药前（0 h）和给药后0.083、0.167、0.333、0.5、0.75、1、1.5、2、3、4、6、8、10 h采血0.3 ml，每个时间点取6只，采用高效液相色谱-质谱法，以盐酸巴马汀为内标，测定次乌头碱的血药浓度。利用DAS2.0.1药动学软件计算药动学参数。结果：次乌头碱检测质量浓度的线性范围为0.1024～100 ng/ml（r＝0.9987），定量限为0.1 ng/ml。其在单用组和联用组大鼠体内的药动学参数tmax分别为（0.50±0.086）、（0.75±0.132）h，t1/2分别为（9.967±1.123）、（3.708±0.507）h，AUC0-10 h分别为（26.087±0.672）、（6.516±1.135）μg·h/L，cmax分别为（6.124±2.312）、（1.592±0.051）μg/L；与单用组比较，联用组大鼠体内次乌头碱的t1/2、AUC0-10 h、cmax均减小，差异有统计学意义（P＜0.05）。结论：大黄可以抑制次乌头碱在大鼠体内的吸收，加快其在体内的消除。

OBJECTIVE：To study the effects of Heishun tablets combined with Rheum palmatum on the pharmacokinetics of hypaconitine in rats. METHODS：Rats were randomly divided into single drug group（Heishun tablets decoction）and drug combi-nation group（Heishun tablets-R. palmatum mixture decoction）,with 18 rats in each group. They were given relevant drugs intragas-trically,by 10 g（medicinal materials）/kg of Heishun tablets. 0.3 ml blood samples were collected before（0 h）and 0.083,0.167, 0.333,0.5,0.75,1,1.5,2,3,4,6,8,10 h after medication with 6 rats at each time point,respectively. The blood concentra-tion of hypaconitine was determined by HPLC-MS using palmatine hydrochloride as internal standard. DAS 2.0.1 software was used to calculate pharmacokinetic parameters. RESULTS：The linear range of hypaconitine was 0.102 4-100 ng/ml （r=0.998 7）,and the limit of quantification was 0.1 ng/ml. The pharmacokinetic parameters of single drug group vs. drug combination group were as follows as tmax of （0.50 ± 0.086） h vs. （0.75 ± 0.132）h;t1/2 of （9.967 ± 1.123） h vs. （3.708 ± 0.507） h;AUC0-10 h of （26.087 ± 0.672） μg·h/L vs.（6.516 ± 1.135） μg·h/L;cmax of （6.124 ± 2.312） μg/L vs. （1.592 ± 0.051） μg/L. Compared with single drug group,t1/2,AUC0-10 h and cmax of hypaconitine were decreased in drug combination group,with statistical significance （P〈0.05）. CONCLUSIONS：R. palmatum can inhibit the absorption of hypaconitine in rats,and speed up the elimination of it in rats.