高脂餐对地塞米松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 dexamethasone in healthy Chinese volunteers

作　　者：王芳[1] 金艺[1] 姜兴颖 杨楠 徐海燕[1] 袁波[1] WANG Fang;JIN Yi;JIANG Xing-ying;YANG Nan;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,沈阳110016

出　　处：《国际药学研究杂志》2020年第2期136-142,共7页Journal of International Pharmaceutical Research

摘　　要：目的研究空腹和高脂餐后服用地塞米松片在人体内药代动力学行为的区别。方法20名志愿者分别在空腹及高脂餐后口服1.5 mg剂量地塞米松片,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计算主要动力学参数,使用SPSS 24软件对主要药动学参数进行统计分析。结果人血浆中地塞米松的质量浓度在0.100~20.0μg/L内线性关系良好;受试者空腹及高脂餐后口服地塞米松片后的主要动力学参数为:Cmax分别为(17.79±4.44)及(12.95±4.05)μg/L,Tmax分别为(0.78±0.49)及(1.58±0.91)h,t1/2分别为(4.15±0.90)及(4.88±1.35)h,AUC0-t分别为(62.08±14.23)及(75.84±26.84)μg·h/L,AUC0-∞分别为(63.29±15.13)及(79.58±30.33)μg·h/L,MRT0-t分别为(4.90±0.82)及(5.93±1.11)h,MRT0-∞分别为(5.39±1.06)及(6.93±1.83)h。对空腹与餐后给药的主要药动学参数采用独立样本t检验进行统计分析。结果表明AUC0-t、AUC0-∞及t1/2空腹组和餐后组无显著性差异(P>0.05),Cmax、Tmax、MRT0-t和MRT0-∞具有显著性差异(P<0.05)。结论高脂餐后服用地塞米松片可显著延后地塞米松达峰时间、延长平均驻留时间,降低达峰浓度,但不影响药物体内暴露量。Objective To investigate the differences in the pharmacokinetics of dexamethasone between fasting and high-fat meals in Chinese volunteers.Methods Twenty volunteers were given a 1.5 mg dose of dexamethasone tablets before and after a highfat meal.After the plasma sample was prepared by protein precipitation,the plasma concentration of dexamethasone was determined by LC-MS/MS.The main pharmacokinetic parameters were calculated with DAS 3.2.1 software.The statistical analysis was carried out with SPSS 24 software.Results The calibration curve for dexamethasone in human plasma showed a good linearity within the concen tration range of 0.100-20.0μg/L.The main pharmacokinetic parameters of dexamethasone for the fasting and high-fat meal conditions were as follows:Cmax(17.79±4.44)and(12.95±4.05)μg/L,Tmax(0.78±0.49)and(1.58±0.91)h,t1/2(4.15±0.90)and(4.88±1.35)h,AUC0-t(62.08±14.23)and(75.84±26.84)μg·h/L,AUC0-∞(63.29±15.13)and(79.58±30.33)μg·h/L,MRT0-t(4.90±0.82)and(5.93±1.11)h,and MRT0-∞(5.39±1.06)and(6.93±1.83)h,respectively.The t-test results showed that there were significant differ ences in Tmax,Cmax,MRT0-t and MRT0-∞(P<0.05)but not the AUC0-t,AUC0-∞and t1/2(P>0.05)between the fasting and high-fat meal groups.Conclusion High-fat meals could significantly delay the time to reach maximum concentration,increase the mean residence time and reduce the peak concentration of dexamethasone,but does not influence the exposure amount.

关 键 词：地塞米松 空腹 高脂餐 药代动力学 液相色谱-串联/质谱 

分 类 号：R969.1[医药卫生—药理学]