芪苈强心胶囊中生物碱在大鼠体内的药动学行为

目的考察芪苈强心胶囊中生物碱在大鼠体内的药动学行为。方法大鼠灌胃给予1.3 g/kg药物混悬液后,于不同时间点(0.083、0.167、0.333、0.667、1、1.5、2、3、4、6、8、12、24 h)取血,HPLC-MS/MS法测定乌头碱、新乌头碱、次乌头碱、苯甲酰乌头原碱、苯甲酰新乌头原碱、苯甲酰次乌头原碱血药浓度,DAS 3.0软件计算药动学参数。结果乌头碱、新乌头碱、次乌头碱、苯甲酰乌头原碱、苯甲酰新乌头原碱、苯甲酰次乌头原碱Tmax分别为0.33、0.17、0.33、1.00、0.67、0.67 h,t1/2分别为18.35、6.23、8.01、18.63、8.23、12.88 h,Cmax分别为1.44、0.52、1.97、1.83、5.84、0.67 ng/mL,AUC0-t分别为7.03、3.95、7.89、8.63、20.13、4.03 h·ng/mL。结论芪苈强心胶囊中生物碱在大鼠体内可迅速吸收,单酯型生物碱(苯甲酰乌头原碱、苯甲酰新乌头原碱、苯甲酰次乌头原碱)体内暴露水平高于双酯型生物碱(乌头碱、新乌头碱、次乌头碱)。

In vivo pharmacokinetic behaviors of alkaloids in Qili Qiangxin Capsules in rats

AIM To investigate the in vivo pharmacokinetic behaviors of alkaloids in Qili Qiangxin Capsules in rats.METHODS Rats were given intragastric administration of 1.3 g/kg drug suspension, after which blood collection was made at different time points(0.083, 0.167, 0.333, 0.667, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h), HPLC-MS/MS was adopted in the plasma concentration determination of aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypacoitine, and the calculation of pharmacokinetic parameters was achieved by DAS 3.0 software.RESULTS Aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, and benzoylhypacoitine demonstrated the Tmax of 0.33, 0.17, 0.33, 1.00, 0.67, 0.67 h, t1/2 of 18.35, 6.23, 8.01, 18.63, 8.23, 12.88 h, Cmax of 1.44, 0.52, 1.97, 1.83, 5.84, 0.67 ng/mL, and AUC0~t of 7.03, 3.95, 7.89, 8.63, 20.13, 4.03 h·ng/mL, respectively.CONCLUSION Alkaloids in Qili Qiangxin Capsules can be rapidly absorbed in rats in vivo, and monoester alkaloids(aconitine, mesaconitine, hypaconitine) display higher in vivo exposure levels than diester alkaloids(benzoylaconine, benzoylmesaconine, benzoylhypacoitine).