二维液相色谱法测定尼美舒利血药浓度并研究其颗粒剂的人体生物利用度

Determination of nimesulide plasma concentration by two-dimensional liquid chromatography and bioavailability of granules in humans

目的采用二维液相色谱法测定尼美舒利血药浓度并评价尼美舒利颗粒剂相对片剂的生物利用度。方法本研究为开放、随机、双周期交叉、口服给药的单中心试验。试验受试者共20人,清洗期为1周。在服药前(0)和口服100 mg的药物后0.25、0.5、1.0、1.5、2.0、2.5、3.0、4.0、5.0、6.0、8.0、10.0、12.0、16.0、24.0 h(共16点)从肘静脉取血4.0 mL用于药物浓度分析。采用二维液相色谱法测定给药后不同时间尼美舒利的血药浓度。利用SPSS 13.0软件计算药动学参数和进行统计分析。结果颗粒剂与片剂的药动学参数如下:AUC0～24分别为(34.783±13.174)和(34.638±11.659)μg·h·m L-1;AUC0～∞分别为(35.624±13.868)和(35.624±12.187)μg·h·m L-1;Cmax分别为(4.986±1.097)和(4.780±1.287)μg·m L-1;tmax分别为(2.1±0.7)和(3.6±1.0)h;t1/2分别为(3.2±1.1)和(3.6±1.1)h;MRT分别为(5.7±1.6)和(7.4±1.7)h;受试制剂对参比制剂的相对生物利用度(以AUC0～24作为评价依据)为(103.6±28.0)%。ln AUC0～24、ln AUC0～∞、ln Cmax的90%可信区间分别为89.1%～111.9%、88.6%～111.2%、98.2%～113.9%。结论二维液相色谱法测定尼美舒利血药浓度快速、准确;颗粒剂与片剂在空腹给药时在人体的吸收量差异无统计学意义,具有生物等效性。

Objective To determine the plasma concentration of nimesulide by two-dimensional liquid chromatography,and evaluate the bioequivalence of nimesulide granules and nimesulide tablets.Methods This study was an open,randomized,double cycle,oral administration single center trial.A total of 20subjects were tested,and the cycle of the double cycle study was one week.Before medication (0),and 0.5,1,1.5,2,2.5,4, 3,5,6,8,10,12,16,and 24h (16time points)after single dose of 100mg of the drug,4mL plasma from the elbow vein was taken for drug concentration analysis.Two-dimensional liquid chromatography was used to determine the plasma concentration of nimesulide at different time after the administration.The pharmacokinetic parameters were calculated and analyzed by SPSS 13.0.Results The main pharmacokinetic parameters of the granules and the tablets were as follows:AUC0~24was (34.783±13.174)and (34.638±11.659)μg·h·mL^-1; AUC0-∞was (35.624±13.868)and (35.624±12.187)μg·h·mL^-1;Cmax (4.986±1.097)and (4.780±1.287) μg·h·mL^-1;tmax was (2.14±0.7)and (3.6±1.0)h;tan was (3.24±1.1)and (3.6±1.1)h;MRT was (5.74±1.6)and (7.44±1.7)h,respectively.The relative bioavailability of granules was (103.64±28)%.The 90%confidential interval of In A UCo -24,In AUC0-∞and In Cmax of the granules was 89.1%--111.9%,88.6%--111.2%,and 98.2%--113.9%,respectively.Conclusion It is fast and accurate to determine the plasma concentration of nimesulide by two-dimensional liquid chromatography.The two nimesulide preparations are bioequivalent.