全三七片混合粉单、多次给药大鼠体内药代动力学研究

Pharmacokinetics study of Quansanqi tablets mixed powder after single and multiple dosing in rats

  • 摘要: 对建立的HPLC-MS/MS法测定SD大鼠血浆中人参皂苷Rb1、人参皂苷Rg1和三七皂苷R1浓度的方法进行方法学验证,并考察全三七片混合粉在大鼠体内单次及多次给药后的药代动力学特征. 将32只SD大鼠随机分为单次给药低、中、高剂量组(剂量分别为103420694138 mg/kg全三七片混合粉)和多次给药组(剂量为2069 mg/kg全三七片混合粉,每天给药1次,连续给药7 d),并于给药前后进行血样采集. 以UPLC-ESI-MS/MS测定血浆样品中的药物浓度,采用非房室模型计算药代参数. 单次给药后,人参皂苷Rb1的平均t1/2明显长于人参皂苷Rg1和三七皂苷R1,平均Cmax、平均AUC0-t亦显著更高. 多次给药组,人参皂苷Rb1、人参皂苷Rg1和三七皂苷R1平均t1/2分为(20 ± 1.7)、(4.7 ± 1.1)、(4.7 ± 1.8) h,平均Cmax分别为(827 ± 141)、(44.1 ± 34.1)、(29.9 ± 20.1) ng/mL,平均AUC0-t分别为(24700 ± 5210)、(306 ± 231)、(201 ± 120) h·ng/mL. 结果表明,人参皂苷Rb1吸收较慢,消除较慢,人参皂苷Rg1和三七皂苷R1吸收与消除均较快. 连续7 d给药后,血浆中人参皂苷Rb1、人参皂苷Rg1和三七皂苷R1可达稳态,且无明显蓄积. AUC0-tCmax无明显性别差异.

     

    Abstract: A developed HPLC-MS/MS method for determining the concentrations of ginsenoside Rb1, ginsenoside Rg1, and notoginsenoside R1 in Sprague-Dawley (SD) rat plasma was methodologically validated, and the pharmacokinetic characteristics of the Quansanqi tablets mixed powder were investigated in rats following single and multiple administrations. Thirty-two SD rats were randomly divided into single-dose low, medium, and high-dose groups (1034, 2069, and 4138 mg/kg Quansanqi tablets mixed powder, respectively) and a multiple-dose group (2069 mg/kg Quansanqi tablets mixed powder, administered once daily for 7 consecutive days). Blood samples were collected before and after administration. Plasma drug concentrations were determined by UPLC-ESI-MS/MS, and pharmacokinetic parameters were calculated using a non-compartmental model. Following a single dose, the mean t1/2 of ginsenoside Rb1 was significantly longer than those of ginsenoside Rg1 and notoginsenoside R1, and its mean Cmax and AUC0-t were also notably higher. In the multiple-dose group, the mean t1/2 values for ginsenoside Rb1, ginsenoside Rg1, and notoginsenoside R1 were (20 ± 1.7), (4.7 ± 1.1), and (4.7 ± 1.8) h, respectively. The mean Cmax values were (827 ± 141), (44.1 ± 34.1), and (29.9 ± 20.1) ng/mL, respectively. And the mean AUC0-t values were (24700 ± 5210), (306 ± 231), and (201 ± 120) h·ng/mL, respectively. The results indicate that ginsenoside Rb1 exhibits slower absorption and elimination, whereas both ginsenoside Rg1 and notoginsenoside R1 are absorbed and eliminated more rapidly. Following 7 consecutive days of administration, the plasma concentrations of ginsenoside Rb1, ginsenoside Rg1, and notoginsenoside R1 reached a steady state with no significant accumulation. No significant sex differences were observed for AUC0-t and Cmax.

     

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