吡硫醇在低氧与常氧环境下大鼠体内的药代动力学研究

Pharmacokinetic comparison of Pyritinol in rats under normoxic and hypoxic condition

目的研究比较吡硫醇在低氧和常氧状态大鼠体内的药代动力学特征。方法将SD大鼠采用数字表法随机分为低氧组与常氧组,低氧动物预处理后进行吡硫醇单次灌胃给药的药代动力学研究。采用本课题组建立的快速灵敏的超高效液相质谱联用测定不同时间的血药浓度,用DAS2.0软件计算药动学参数,并用SPSS13.0软件进行统计学分析。结果吡硫醇在常氧和低氧大鼠体内的主要药动学参数分别为:AUC_(0-t)(88.26±9.86)ng·h·mL^(-1)和(80.67±8.95)ng·h·mL^(-1);MRT_(0-t)(4.14±0.32)h和(3.67±0.26)h;t_(1/2)(3.72±1.82)h和(3.14±1.42)h;t_(max)(0.58±0.20)h和(0.67±0.26)h;C_(max)(30.12±2.36)ng/mL和(20.05±1.31)ng/mL。与常氧状态大鼠的药动学参数相比,低氧状态下吡硫醇在大鼠体内的C_(max)和MRT_(0-t)有显著性降低,而其他主要药动学参数差异均无统计学意义。结论低氧影响药物在大鼠体内达峰浓度,进而可影响药物的稳态血药浓度、治疗效果和毒性反应。

Objective To determine and compare the pharmacokinetic parameters of Pyritinol in rat plasma under normoxic and hypoxic conditions.Methods An effective and rapid ultra-performance liquid chromatography with tandem mass spectrometry （UPLC-MS/MS） method with positive electrospray ionization source was successfully developed and validated for quantification of Pyritinol in rat plasma.Sprague-Dawley rats were randomly divided into the hypoxia and normoxic groups.Each rat obtained a single dose of Pyritinol through intragastric administration.The plasma samples were drawn through jugular veins to measure the drug concentrations at different times.The pharmacokinetics parameters were processed via the DAS 2.0 software,and the comparison of main pharmacokinetic parameters in rats between normoxic and hypoxic groups was calculated by the SPSS software via an independent sample t test method.Results The main pharmacokinetic parameters of Pyritinol between the hypoxia and the normoxic rats were as follows： the AUC（0-t） （88.26±9.86） ng·h·mL^-1 and （80.67±8.95）ng·h·mL^-1,MRT（0-t） （4.14±0.32）h and （3.67±0.26）h,t1/2 （3.72±1.82） h and （3.14±1.42）h,tmax （0.58±0.20）h and （0.67±0.26）h,Cmax（30.12±2.36）ng/mL and （20.05±1.31）ng/mL,respectively.The values of Cmax and MRT（0-t） for Pyritinol in hypoxic rats were statistically lower than that in normoxic rats,and other main pharmacokinetic parameters did not have significant differences.Conclusion Hypoxia affects drug peak concentration in rats,and furthermore affects the steady-state blood concentrations of drugs,which could interfere the therapeutic effect and toxic reaction.