法罗培南钠颗粒的人体药动学研究

Pharmacokinetics of faropenem sodium granules in Chinese healthy volunteers

目的:建立液相色谱串联质谱法(LC-MS-MS)测定人血浆中法罗培南浓度,研究法罗培南钠颗粒在健康中国志愿者体内的药动学行为。方法:选取10名健康志愿者(男女各半)口服100mg的法罗培南钠颗粒,进行单次给药及多次给药达稳态后的药动学研究,采集静脉血样,血浆样品用三氯乙酸沉淀蛋白后用液相色谱串联三级四极杆质谱检测原形药物浓度。结果:法罗培南在5.02～6528ng/mL范围内线性关系良好,最低检测限为2ng/mL(S/N≈3),平均回收率>90%,批间批内RSD均小于10%。计算得到单次口服100mg法罗培南钠颗粒的主要药动学参数:Cmax为(2322±1345)ng/mL,tmax为(0.78±0.32)h,t1/2为(0.98±0.34)h,MRT为(1.8±0.4)h,AUC0-8为(3953±1906)ng·mL-1.h,AUC0-∞为(3980±936)ng·mL-1.h。连续多次口服法罗培南钠颗粒达稳态后,测得法罗培南钠的主要药代动力学参数:Cssmax为(2870±1178)ng/mL,Cssmin为(72±55)ng/mL,Cssav为(658±439)ng/mL,tmax为(0.80±0.20)h,t1/2为(0.91±0.16)h,AUCss为(5263±3513)ng·mL-1.h。结论:LC-MS-MS法操作简便快速,灵敏度高,结果准确,适合人血浆中法罗培南的浓度测定;多次给药达稳态时主要药动学参数与单次给药基本一致,统计分析差异无统计学意义,表明法罗培南钠在体内基本无积蓄。

AIM：To establish an LC-MS-MS method for determination of faropenem in human plasma and investigate the pharmacokinetics of faropenem sodium granules in Chinese healthy volunteers. METHODS：10 Healthy volunteers （5 male,5 female） were given a 100 mg dose of faropenem sodium granules. The single dose and multiple dose experiment were carried out. Blood samples were collected from elbow vein,and trichloroacetic acid was used as protein precipitation agents. The analyte were detected by HPLC tandem triple stage quadrupole MS detector. RESULTS：Faropenem had a good linear range of 5.02-6528 ng/mL,with a limit of detection 2 ng/mL. The average recovery was more than 90%. The average RSD was within 10% for intra-batch and inter-batch precision. The major pharmacokinetic parameters of single dose administration were as follows：Cmax （2322±1345） ng/mL; tmax （0.78±0.32） h; t1/2（0.98±0.34） h; MRT（1.8±0.4） h;AUC0-8（3953±1906） ng·mL^-1·h;AUC0-∞（3980±1936） ng·mL^-1·h,and multiple dose administration as follows：Css_max （2870±1178） ng/mL; Css_min （72±55） ng/mL;Css_av（658±439） ng/mL;tmax（0.80±0.20） h;t1/2（0.91±0.16） h;AUCss（5263±3513）ng·mL^-1·h. CONCLUSION：The LC-MS-MS method is convenient,fast,sensitive and accurate. It is suit for determination of faropenem in human plasma. For the main pharmacokinetic parameters,there is no significant difference of between single dose and multiple doses,which indicates that there is not accumulation phenomenon.