高脂高热量饮食对中国健康受试者口服甲硝唑片药代动力学的影响  

Effect of high fat diet intake on pharmacokinetics of metronidazole tablets in healthy Chinese volunteers

作　　者：赵娜[1] 郭彩会[1] 刘亚丽 宋浩静[1] 史犇 胡义亭[1] 贾彩云[1] 董占军[1] ZHAO Na;GUO Cai-hui;LIU Ya-li;SONG Hao-jing;SHI Ben;HU Yi-ting;JIA Cai-yun;DONG Zhan-jun(Phase I Clinical Laboratory,Hebei General Hospital,Shijiazhuang 050051,Hebei Province,China;Shijiazhuang Siyao Co.,Ltd.,Shijiazhuang 050051,Hebei Province,China;Suzhou Guochen Biotek Company Limited,Suzhou 215104,Jiangsu Province,China)

机构地区：[1]河北省人民医院Ⅰ期临床研究室,河北石家庄050051 [2]石家庄四药有限公司,河北石家庄050051 [3]苏州国辰生物科技股份有限公司,江苏苏州215104

出　　处：《中国临床药理学杂志》2024年第1期102-106,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价在空腹和高脂高热量饮食情况下甲硝唑片在中国健康受试者中的药代动力学特征。方法本方案按单中心、随机、开放、单剂量的试验设计。空腹和高脂高热量饮食条件下共入组47例中国健康受试者,单次口服甲硝唑片200 mg,给药前后按规定时间点采集静脉血样。用高效液相色谱串联质谱法测定血浆中甲硝唑的浓度并计算药代动力学参数。结果甲硝唑片空腹和高脂高热量饮食后的主要药代动力学参数如下:C_(max)分别为(4799.13±1195.32)和(4044.17±773.98)ng·mL^(-1),t_(max)分别为1.00和2.25 h,t1/2分别为(9.11±1.73)和(9.37±1.79)h,AUC_(0-t)分别为(5.59±1.19)×10^(4)和(5.51±1.18)×10^(4) ng·mL^(-1)·h,AUC_(0-∞)分别为(5.79±1.33)×10^(4)和(5.74±1.32)×10^(4) ng·mL^(-1)·h;高脂饮食后服药较空腹条件下服药,t_(max)延迟1.25 h(P<0.01),C_(max)、AUC_(0-t)、AUC_(0-∞)虽有不同程度的较少或降低,但影响较小(均P>0.05)。结论高脂餐饮食对甲硝唑的药代动力学参数影响较小,虽然不会显著改变药物的吸收程度,但是会使达峰时间明显延迟。Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:C_(max) were(4799.13±1195.32)and(4044.17±773.98)ng·mL^(-1);t_(max) were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC_(0-t) were(5.59±1.19)×10^(4) and(5.51±1.18)×10^(4) ng·mL^(-1)·h;AUC_(0-∞)were(5.79±1.33)×10^(4) and(5.74±1.32)×10^(4) ng·mL^(-1)·h.Compared to the fasting state,the t_(max)of the drug taken after a high fat diet was delayed by 1.25 h(P<0.01),C_(max),AUC_(0-t),AUC_(0-∞)were less or decreased in different deg re es,but the effects were small(all P>0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.

关 键 词：甲硝唑片 高脂饮食 药代动力学 食物效应 

分 类 号：R978[医药卫生—药品]