艾迪注射液对大鼠体内紫杉醇药代动力学的影响

Influence of aidi injection on pharmacokinetics of paclitaxel in rats

目的:研究艾迪注射液对大鼠体内紫杉醇药代动力学参数的影响。方法:12只SD大鼠,雌雄各半,体重180~220 g,随机分为对照组和实验组,实验组连续5 d给予艾迪注射液1 mL·kg^(-1),每天1次,对照组给予等量生理盐水代替。最后一次给药后30 min两组均给予紫杉醇注射液12 mL·kg^(-1),并于给药后0、0.5、1、2、4、8、12、24和48 h分别自眼眶取血0.2 mL。分离血浆后采用液质联用的方法测定血浆中紫杉醇的含量,采用DAS2.0软件分析药代动力学参数,采用SPSS软件进行统计学分析。结果:对照组和实验组的C_(max)分别为(39 555.69±1 728.70)和(79 957.62±18 067.58)μg·L^(-1)(P<0.05);AUC_(0→t)分别为(28 616.24±7 059.78)和(76 066.42±32 518.88)μg·L^(-1)·h(P<0.05);t_(1/2)分别为(3.49±1.17)和(5.99±0.75)h(P<0.05);其他参数差异无显著性。结论:艾迪注射液可显著增加大鼠体内紫杉醇的C_(max)和AUC_(0→t)并降低t_(1/2)。

Objective: To explore the influence on pharmacokinetics parameters of paclitaxel after pretreatment with aidi injection in rats. Methods: 12 SD rats, half male and half female with body weight of 180~220 g,were randomly divided into control and experimental groups. Rats in experimental group were pretreated with aidi injection at the dose of 1 mL·kg^(-1)once a day for consecutively 5 days, while rats in control groups were treated with saline solution instead. 30 minutes after the last treatment, both groups were treated with paclitaxel at the dose of 12 mL·kg^(-1). Blood samples were obtained from rat eyes at 0, 0.5, 1, 2, 4, 8, 12, 24 and 48 h after administration. LC-MS/MS was used to determine plasma concentration of paclitaxel. Pharmacokinetic parameters were calculated by DAS2.0 software and SPSS software was used for statistical analysis. Results: C_(max) levels of paclitaxel in rats of control and experimental groups was(39 555.69±1 728.70) and(79 957.62±18 067.58)μg·L^(-1) respectively(P < 0.05). AUC_(0→t) in control and experimental group was(28 616.24±7 059.78) and(76 066.42±32 518.88)μg·L^(-1)·h(P < 0.05) while t_(1/2) in control and experimental group was(3.49±1.17) and(5.99±0.75) h(P < 0.05). No significant difference was detected in other pharmacokinetic parameters of the both groups. Conclusion: aidi injection could significantly increase C_(max) and AUC_(0→t) while decrease t_(1/2) of paclitaxel.