高脂餐对多潘立酮在中国健康受试者体内药代动力学行为的影响  

Effect of high-fat meal on the pharmacokinetics of domperidone in healthy Chinese volunteers

作　　者：董倩楠 金艺[1] 王琳[1] 陈晨[1] 徐海燕[1] 袁波[1] DONG Qian-nan;JIN Yi;WANG Lin;CHEN Chen;XU Hai-yan;YUAN Bo(School of Pharmacy , Shenyang Pharmaceutical University, Shenyang 110016, China)

机构地区：[1]沈阳药科大学药学院

出　　处：《国际药学研究杂志》2019年第2期130-136,共7页Journal of International Pharmaceutical Research

摘　　要：目的研究高脂餐对多潘立酮片在中国健康受试者体内药代动力学行为的影响。方法采用随机、开放、双周期交叉试验设计,17名健康受试者各自在空腹及高脂餐后30 min后单剂量口服多潘立酮片1片(规格:10 mg/片),于给药前及给药后0.17、0.33、0.5、0.75、1、1.5、2、2.5、3、4、6、8、10、12、24、48 h收集血液样品并提取血浆,血浆样品经蛋白沉淀法处理后采用LC-MS/MS法进行检测,使用DAS 3.2.2计算主要药代动力学参数,使用SPSS 24软件对主要药代动力学参数进行统计分析。结果人血浆中多潘立酮在0.104~40.0μg/L范围内线性关系良好;受试者空腹及高脂餐后口服多潘立酮片后的主要药代动力学数据为:Cmax分别为(18.41±6.96)及(14.52±5.79)μg/L,Tmax分别为(0.70±0.33)及(1.70±1.10)h,T1/2分别为(10.48±2.01)及(9.52±1.33)h,AUC0-t分别为(62.96±21.71)及(78.25±17.74)μg·h/L,AUC0-∞分别为(65.34±22.13)及(80.10±17.87)μg·h/L。对空腹与高脂餐后给药的主要药动学参数采用配对t检验进行统计分析,两者Cmax及T1/2无显著性差异,高脂餐组Tmax明显延后(P<0.01),AUC显著升高(P<0.05)。结论高脂饮食可显著延后多潘立酮的达峰时间,并可明显提高多潘立酮的生物利用度。Objective To investigate the effect of high-fat meal on the pharmacokinetics of domperidone(Dom)in healthy Chinese volunteers after single oral dose of Dom tablet. Methods According to a random opening,two-period crossover design,17 healthy volunteers received a 10 mg dose of Dom tablet before and after a high-fat meal. The blood sample was collected prior to dosing and at the 0.17,0.33,0.5,0.75,1,1.5,2,2.5,3,4,6,8,10,12,24,and 48 h of dosing. The plasma samples were prepared by the protein precipitation method. The concentrations of Dom in plasma were determined by LC-MS/MS. The main pharmacokinetic parameters were calculated with the DAS 3.2.2 software. The statistical analysis was carried out with the SPSS 24 software. Results The calibration curve of Dom in human plasma showed a good linearity within the concentration range of 0.104-40.0 μg/L. The main pharmacokinetic parameters for the Dom dosed before and after a high-fat meal were as follows:Cmax(18.41±6.96)and(14.52±5.79)μg/L,Tmax(0.70±0.33)and(1.70±1.1)h,T1/2(10.48±2.01)and(9.52±1.33)h,AUC0-t(62.96±21.71)and(78.25±17.74)μg·h/L,and AUC0-∞(65.34±22.13)and(80.10±17.87)μg·h/L,respectively. The paired-sample t-test was performed for the statistical analysis of the pharmacokinetic parameters for the fasting and high-fat meal groups. There was no significant difference in Cmaxand T1/2,while the difference in Tmax(P<0.01),AUC0-tand AUC0-∞(P<0.05)were significant,all between the two groups. Conclusions High-fat meal could significantly delay the time to reach maximal concentration of Dom and increase the bioavailability of Dom.

关 键 词：多潘立酮 高脂饮食 药代动力学 人血浆 LC-MS/MS 

分 类 号：R969.1[医药卫生—药理学]