高脂饮食对阿莫西林在中国健康人体内药代动力学的影响

Effect of high-fat diet intake on pharmacokinetics of amoxicillin and clavulanate potassium tablet in healthy Chinese volunteers

目的 观察中国健康受试者在空腹和高脂高热量饮食情况下口服阿莫西林克拉维酸钾片对阿莫西林的药代动力学影响。方法 71例健康受试者分别在空腹或高脂饮食条件下单剂量口服阿莫西林克拉维酸钾片0.375 g,分别在不同时间点采集静脉血样。用高效液相色谱串联质谱法测定人血浆中阿莫西林的浓度,用PhoenixWinNonlin 8.0软件按非房室模型计算药代动力学参数。结果 空腹和高脂饮食后阿莫西林的主要药代动力学参数:C_(max)分别为(5 105.00±1 444.00)、(4 593.00±1 327.00)ng·mL^(-1),餐后/空腹比值89.40%,90%的置信区间(79.55%~100.19%);t_(1/2)分别为(1.52±0.16)、(1.39±0.22)h;AUC_(0-t)分别为(12 969.00±1 841.00)、(11 577.00±1 663.00)ng·mL^(-1)·h,餐后/空腹比值89.20%,90%的置信区间(83.92%~94.28%);AUC_(0-∞)分别为(13 024.00±1 846.00)、(11 532.00±1 545.00)ng·mL^(-1)·h,餐后/空腹比值88.60%,90%的置信区间(83.48%~93.50%);T_(max)中位数(范围)分别为1.63 (0.75,3.00)和2.50 (0.75,6.00) h,餐后服药的T_(max)延迟(P<0.01)。结论 高脂饮食后服药较空腹条件下服药,阿莫西林T_(max)明显延迟,C_(max)、AUC_(0-t)及AUC_(0-∞)变化不明显,说明食物可延缓阿莫西林的吸收,但不影响其吸收程度。

Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g) on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using Phoenix Win Nonlin 8.0software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00) ng · mL^(-1),and postprandial-fasting ratio 89.40%,90% confidence interval(79.55%-100.19%);t_(1/2) were(1.52±0.16),(1.39±0.22) h;AUC_(0-t) were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL^(-1)·h,and postdietary/fasting ratio 89.20%,90% confidence interval(83.92%-94.28%);AUC_(0-∞) were(13 024.00±1 846.00),(11 532.00±1 545.00) ng · mL^(-1)·h,and postprandial-fasting ratio 88.60%,90% confidence interval(83.48%-93.50%).The median T_(max)(range) were1.63(0.75,3.00) and 2.50(0.75,6.00) h,respectively,and the T_(max) of postprandial medication was delayed(P <0.01).Conclusion Compared with fasting condition,amoxicillin T_(max) was significantly delayed after high fat diet,while C_(max),AUC_(0-t) and AUC_(0-∞) were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.