高蛋白高纤维高脂肪饮食对4种药物在大鼠体内药动学的影响

目的：考察健康大鼠在长期给予不同饮食类型之后对4种药物在体内的药动学影响。方法：SPF级SD大鼠随机分成4组（高蛋白组A、高纤维组B、高脂肪组C、标准饮食组D），分别给予不同饮食类型的食物，进行多种药物（左氧氟沙星、右美沙芬、美托洛尔、二甲双胍）的药动学实验，HPLC-MS/MS分析药物浓度，WinNonlin计算药动学参数，SPSS软件对不同组药动学参数进行统计学分析。结果：右美沙芬和美托洛尔的主要药动学参数C_max、AUC_0-∞、CL、Vd等组间存在显著性差异（P<0.05）；二甲双胍和左氧氟沙星的主要药动学参数C_max、AUC_0-∞、CL组间差异无统计学意义（P>0.05），其中左氧氟沙星的Vd高脂肪组与其标准组差异具有统计学意义。结论：不同饮食习惯会对药物的药动学产生影响，对不同的药物影响不同，可以成为个体之间药动学差异的一种解释，为后续研究饮食习惯影响药动学的具体因素（如药物的代谢酶、转运体等）提供依据。

Influence of diets with high protein,fiber and fat on pharmacokinetics of 4 drugs in rats

OBJECTIVE To explore the influence of long term diets with high protein,fiber and fat on pharmacokinetics of 4 drugs in healthy rats.METHODS FPF rats were randomly divided into four group (group A,high protein; group B,high fiber; group C,high fat; group D,standard) and received different diets,and then pharmacokinetic experiments of 4 drugs (levofloxacin,dextromethorphan,metoprolol,metformin) were performed,with drug concentrations analyzed by HPLC-MS/MS,pharmacokinetic parameters calculated by WinNonlin,pharmacokinetic parameters statistically analyzed by SPSS software.RESULTS There were significant differences in main pharmacokinetic parameters (C_max,AUC_0-∞,CL and Vd) of dextromethorphan and metoprolol (P<0.05),no significant difference in pharmacokinetic parameters except Vd between levofloxacin and metformin (P>0.05).CONCLUSION Different dietary habits have different influences on pharmacokinetic parameters of different drugs,which may explain individual pharmacokinetic differences,and provide a reference for subsequent studies on specific factors (metabolism enzymes,transporter,etc.of drugs) for dietary influences.