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

关键词:  双嘧达莫  高脂饮食  药动学  食物效应

Key words:  dipyridamole  high-fat diet  pharmacokinetics  pharmacokinetics  food effect

摘要:

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。

Abstract:

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: C_max were (594.69±172.14) and (333.64±167.18) ng·mL^-1, fasting C_max decreased by 43.9%(P<0.01); t_1/2were (9.87±4.21) and (10.57±3.75) h; AUC_0-twere (1 733.22±715.49) and (1 268.61±571.07) ng·mL^-1·h; AUC_0-∞ were (1 801.69±707.61) and (1 353.64±602.29) ng·mL^-1·h; AUC_0-t and AUC_0-∞ decreased by 26.8% and 24.9% respectively after meals compared with fasting(P<0.01), median T_max (range) were 0.75[0.50, 5.00] h and 1.50[0.49, 4.52] h. CONCLUSION Compared with fasting condition, C_max,AUC_0-t and AUC_0-∞ were significantly decreased after taking the medication after lipid diet, and T_max was significantly delayed, indicating that food has a significant effect on the absorption rate and degree of dipyridamole tablets.