吡嘧司特钾片在中国健康志愿者空腹/餐后的生物等效性研究  

Study on bioequivalence evaluation of Pemirolast potassium tablets in Chinese healthy volunteers on an empty stomach/after meals

作　　者：马宜明[1] 胡旺 张峰 张文 赵胜龙 曹阳 谢晶 周焕[2,3] 黄顺旺 MA Yi-ming;HU Wang;ZHANG Feng;ZHANG Wen;ZHAO Sheng-long;CAO Yang;XIE Jing;ZHOU Huan;HUANG Shun-wang(Dept of Pharmacy,the First Affiliated Hospital of Anhui Medical University,Hefei 230022,China;National Drug Clinical Trial Institution,the First Affiliated Hospital of Bengbu Medical College,Bengbu Anhui 233000,China;Key Laboratory of Innovative Pharmaceutical Research and Clinical Evaluation Jointly Constructed by Anhui,Bengbu Anhui 233000,China;Hefei Innovative Medical Technology Co.,Ltd,Hefei 230088,China)

机构地区：[1]安徽医科大学第一附属医院药剂科,安徽合肥230022 [2]蚌埠医学院第一附属医院临床试验研究中心 [3]创新药物药学研究与临床评价安徽省联合共建学科重点实验室,安徽蚌埠233000 [4]合肥创新医药技术有限公司,安徽合肥230088

出　　处：《中国药理学通报》2024年第6期1075-1081,共7页Chinese Pharmacological Bulletin

基　　金：创新药物药学研究与临床评价安徽省联合共建学科重点实验室项目(No皖科基地秘[2023]108号)。

摘　　要：目的比较单次空腹与餐后条件下吡嘧司特钾片在中国健康受试者体内的药代动力学,评价受试制剂(T)和参比制剂(R)的生物等效性。方法采用随机、开放、单剂量、两周期、双交叉生物等效性试验设计,空腹组与餐后组各入组26名与30名受试者,每周期在空腹状态或餐后状态下服用受试制剂与参比制剂10 mg,在给药周期前后按设计的时间点采集静脉血。用高效液相质谱联用法(LC-MS/MS)测定血浆中的吡嘧司特钾浓度,用Phoenix TM WinNonlin(8.3)软件计算药代动力学参数,对两制剂进行生物等效性分析。结果空腹单次口服给药受试制剂和参比制剂的t 1/2分别为(4.44±0.91)h和(4.49±0.93)h,t max中位数分别为(1.96±1.29)h和(2.18±1.25)h,C max分别为(867.12±205.56)μg·L^(-1)和(863.35±172.03)μg·L^(-1),AUC 0-t分别为(5513.23±1463.67)h·μg·L^(-1)和(5661.32±1628.65)h·μg·L^(-1),AUC 0-∞分别为(5699.81±1477.68)h·μg·L^(-1)和(5849.44±1644.75)h·μg·L^(-1);受试者的主要药代动力学参数C max、AUC 0-t、AUC 0-∞的90%置信区间的统计结果分别为92.49%~107.53%、94.71%~100.67%和95.28%~100.27%,均在80.00%~125.00%范围内,空腹口服受试制剂与参比制剂安全性良好;餐后单次口服给药受试制剂和参比制剂的t 1/2分别为(4.46±0.78)h和(4.51±0.84)h,t max中位数分别为(3.08±1.36)h和(3.28±1.28)h,C max分别为(683.83±111.87)μg·L^(-1)和(689.77±110.24)μg·L^(-1),AUC 0-t分别为(5695.99±1566.05)h·μg·L^(-1)和(5773.60±1551.04)h·μg·L^(-1),AUC 0-∞分别为(5914.06±1551.86)h·μg·L^(-1)和(5967.30±1552.89)h·μg·L^(-1);C max、AUC 0-t、AUC 0-∞的90%置信区间统计结果分别为93.56%~104.69%、96.43%~100.83%和97.29%~101.14%,均在80.00%~125.00%范围内,餐后口服受试制剂与参比制剂安全性良好。结论在空腹与餐后的单次口服给药条件下,两种吡嘧司特钾片具有较好的生物等效性。Aim To compare the pharmacokinetics of pemirolast potassium tablets in healthy subjects in China under single fasting and postprandial conditions,and to evaluate the bioequivalence of the test preparation(T)and the reference preparation(R).Methods A randomized,open-ended,single-dose,two-cycle,double-cross bioequivalence trial design was adopted,and 26 and 30 subjects were enrolled in the fasting group and the postprandial group,respectively,and 10 mg of the test preparation and the reference preparation were taken in the fasting or postprandial state each cycle,and venous blood was collected at the designed time points before and after the administration cycle.The concentration of pemirolast potassium in plasma was determined by LC-MS/MS method,and the pharmacokinetic parameters were calculated with Phoenix TM WinNonlin(8.3)software,and the bioequivalence analysis of the two preparations was performed.Results The t 1/2 of the test preparation and the reference preparation was(4.44±0.91)h and(4.49±0.93)h,respectively;the median t max was(1.96±1.29)h and(2.18±1.25)h,respectively;the C max was(867.12±205.56)μg·L^(-1) and(863.35±172.03)μg·L^(-1),respectively;the AUC 0-t was(5513.23±1463.67)h·μg·L^(-1) and(5661.32±1628.65)h·μg·L^(-1),respectively;AUC 0-∞was(5699.81±1477.68)h·μg·L^(-1) and(5849.44±1644.75)h·μg·L^(-1),respectively.The statistical results of the 90%confidence intervals of the main pharmacokinetic parameters C max,AUC 0-t,and AUC 0-∞was 92.49%~107.53%,94.71%~100.67%and 95.28%~100.27%,respectively,all of which were within the range of 80.00%~125.00%,and the safety of the tested preparation and the reference preparation was good when taken orally on an empty stomach.The t 1/2 of single oral administration after prandial administration of the tested preparation and the reference preparation was(4.46±0.78)and(4.51±0.84)h,respectively;the median t max was(3.08±1.36)h and(3.28±1.28)h,respectively;the C max was(683.83±111.87)μg·L^(-1) and(689.77±110.24)μg·L^(-1),respective

关 键 词：吡嘧司特钾片 健康受试者 药代动力学 生物等效性 

分 类 号：R195[医药卫生—卫生统计学] R333[医药卫生—卫生事业管理] R452[医药卫生—公共卫生与预防医学] R916.4R969.1