救必应总三萜主要成分在正常和高脂血症大鼠体内的药动学比较

目的比较救必应总三萜主要成分在正常和高脂血症大鼠体内的药动学行为。方法 SD大鼠随机分为正常组和模型组,模型组制备高脂血症大鼠模型,各组单次ig救必应总三萜后于不同时间点取血。采用超高效液相色谱串联质谱(UPLC-MS/MS)测定大鼠血浆中冬青苷O、oblonganoside I、rotundinoside C、ilexside II、长梗冬青苷、苦丁冬青苷H、毛冬青皂苷A_1、竹节参皂苷IVa、救必应酸、rotundanonic acid、冬青素A的浓度,将血药浓度和时间数据导入DAS 2.0软件中以非房室模型拟合药动学参数。结果苷元的吸收速度显著高于三萜皂苷,皂苷含糖的数目越多吸收入血的速度越慢。救必应酸在正常和高脂血症大鼠体内的达峰浓度(C_(max))分别为3 257.9、2 173.8 nmol/L,药-时曲线下面积(AUC_(0～t))分别为29 897.6、24 501.3 nmol·h/L,远超其他10个成分的总和。与正常组相比,模型组大部分成分的达峰时间(t_(max))延长,C_(max)、AUC_(0～t)降低。结论救必应总三萜主要成分在正常和高脂血症大鼠体内的药动学行为存在显著差异,救必应酸为口服总三萜后大鼠体内的主要暴露成分。

Pharmacokinetic comparisons of main triterpenoids from Ilicis Rotundae Cortex in normal and hyperlipidemia rats

Objective To compare the pharmacokinetic behavior of main triterpenoids in normal and hyperlipidemia rats after ig total triterpenoids from Ilicis Rotundae Cortex. Methods SD rats were randomly divided into normal group and model group, a hyperlipidemia rat model was prepared in model group, and blood was taken at different time points after a single ig total triterpenoids in each group. Normal and hyperlipidemia rats were given a single oral dose of total triterpenoids of Ilicis Rotundae Cortex. The plasma concentrations of ilexoside O, oblonganoside I, rotundinoside C, ilexside II, pedunculoside, kudinoside H, ilexsaponin A₁, chikusetsusaponin IVa, rotundic acid, rotundanonic acid and ilexgenin A were quantified by UPLC-MS/MS method. The major pharmacokinetic parameters were calculated using non-compartmental analysis with DAS 2.0 software. Results The absorption rate of aglycone was significantly higher than that of saponin. The rate of absorption into blood was significantly reduced with the increasing of the number of sugar groups in saponin. The C_max of rotundic acid in normal and hyperlipidemia groups were 3 257.9 and 2 173.8 nmol/L, and the corresponding AUC_0−t were 29 897.6 and 24 501.3 nmol·h/L, respectively, which was far more than the sum of the other 10 analytes. Compared with normal group, the t_max, C_max and AUC_0−tof most analytes in hyperlipidemia group were delayed or decreased. Conclusion The pharmacokinetics of 11 analytes exhibited significant differences between two groups. Rotundic acid was the main compounds exposing in normal and hyperlipidemia rat plasma.