高脂饮食对双嘧达莫在中国健康人体内药动学的影响

Effect of High-fat Diet Intake on Pharmacokinetics of Dipyridamole Tablet in Healthy Chinese Volunteers

目的观察中国健康受试者空腹和高脂高热量饮食情况下口服双嘧达莫片的药动学特征。方法75名健康受试者分别在空腹或高脂饮食条件下单剂量口服双嘧达莫片25 mg,分别在不同时间点采集静脉血样。采用LC-MS/MS测定人血浆中双嘧达莫的浓度,用PhoenixWinNonlin 8.0软件按非房室模型计算药动学参数。结果空腹和高脂饮食后双嘧达莫片的主要药动学参数如下:C_(max)分别为(594.69±172.14),(333.64±167.18) ng·mL^(-1),餐后较空腹C_(max)降低了43.9%(P<0.01);t_(1/2)分别为(9.87±4.21),(10.57±3.75) h;AUC_(0-t)分别为(1 733.22±715.49),(1 268.61±571.07) ng·mL^(-1)·h,AUC_(0-∞)分别为(1 801.69±707.61),(1 353.64±602.29) ng·mL^(-1)·h,餐后较空腹AUC_(0-t)及AUC_(0-∞)分别降低26.8%,24.9%(P<0.01);T_(max)中位数(范围)分别为0.75[0.50,5.00]h和1.50[0.49,4.52]h,餐后服药的T_(max)明显延迟(P<0.01)。结论高脂饮食后服药较空腹条件下服药,C_(max)、AUC_(0-t)及AUC_(0-∞)均明显降低,T_(max)明显延迟,说明食物对双嘧达莫片的吸收速度、吸收程度均有显著影响。

OBJECTIVE To evaluate the effects of high-fat diet on the pharmacokinetics of dipyridamole in Chinese healthy adult subjects.METHODS All of 75 healthy subjects were assigned to receive single dose of dipyridamole tablet 25 mg in either fasting or high-fat diet state,and blood samples were taken at different time points,respectively.Plasma concentrations of dipyridamole were determined by HPLC-MS/MS.RESULTS The main pharmacokinetic parameters of dipyridamole in fasting state and high-fat diet state were as follows:Cmax were(594.69±172.14)and(333.64±167.18)ng·mL-1,fasting Cmax decreased by 43.9%(P<0.01);t1/2 were(9.87±4.21)and(10.57±3.75)h;AUC0-t were(1733.22±715.49)and(1268.61±571.07)ng·mL-1·h;AUC0-∞were(1801.69±707.61)and(1353.64±602.29)ng·mL-1·h;AUC0-t and AUC0-∞decreased by 26.8%and 24.9%respectively after meals compared with fasting(P<0.01),median Tmax(range)were 0.75[0.50,5.00]h and 1.50[0.49,4.52]h.CONCLUSION Compared with fasting condition,Cmax,AUC0-t and AUC0-∞were significantly decreased after taking the medication after lipid diet,and Tmax was significantly delayed,indicating that food has a significant effect on the absorption rate and degree of dipyridamole tablets.