低氧与常氧状态下芍药苷在大鼠体内的药代动力学比较

Pharmacokinetic comparison of paeoniflorin in rats under normoxic and hypoxic conditions

目的研究比较在低氧与常氧条件下芍药苷在大鼠体内的药代动力学特征。方法建立了高效快速的超高效液相色谱质谱联用法测定大鼠血浆中的芍药苷浓度。SD大鼠随机分为低氧与常氧组（n=6）,芍药苷灌胃给药,剂量为80 mg/kg,测定不同时间点的大鼠血浆药物浓度,计算其主要药代动力学参数,并进行统计学分析。结果在1~1000 ng/ml浓度范围内,血浆中芍药苷的线性关系和稳定性良好,定量下限为1 ng/ml,日内与日间差异均〈15%。芍药苷在低氧组和常氧组大鼠体内的主要药代动力学参数分别为：AUC_（（0-t））26 600.7和35 702.4 ng·min/ml;MRT_（（0-t））127.2和109.7 min;T_（1/2） 111.6和108.6 min;T_（max） 50.8和35.0 min;C_（max） 176.9和332.7 ng/ml。与常氧状态的大鼠药代动力学参数相比较,低氧状态下芍药苷在大鼠体内的药代动力学参数Cmax和AUC均有显著性降低。结论低氧状态下芍药苷在大鼠体内的药代动力学特征发生改变,结果为芍药苷的给药方案优化和调整提供了重要的实验依据。

Objective To study and compare the pharmacokinetic characteristics of paeoniflorin in rats under hypoxic and normoxic conditions. Methods A highly effective and rapid ultra-performance liquid chromatography with tandem mass spectrometry（UPLC-MS/MS）method with multiple-reaction monitoring scanning via electrospray ionization source was successfully developed and validated for quantitation of paeoniflorin in rat plasma. A total of 12 SD rats were randomly divided into the hypoxic and normoxic groups. Each rat was received a single dose of paeoniflorin with 80 mg/kg through intragastric administration. The blood samples were drawn from the jugular veins to measure the plasma drug concentrations in rats at different time points. The pharmacokinetic parameters were processed by DAS software. The statistical analysis was carried out by using SPSS software according to independent sample t test. Results The main pharmacokinetic parameters of paeoniflorin between the hypoxia and the normoxic rats were：AUC_（（0- t））26600.7 and 35 702.4 ng·min/ml,MRT_（（0-t））127.2 and 109.7 min,T1/2111.6 and 108.6 min,T_（max）50.8 and 35.0 min,and C_（max）176.9 and332.7 ng/ml,respectively. The Cmaxand AUC of paeoniflorin in hypoxia rats were significantly reduced,indicating that there was a statistical difference in in vivo drug level. Conclusion The pharmacokinetic behavior of paeoniflorin displayed some changes between the hypoxic and the normoxic rats. Current results provide some experiment basis to optimization and adjustment of dosage regimen for paeoniflorin preparation in clinical practice.