脂质饮食对诺氟沙星在Beagle犬体内药动学的影响

Effects of Lipid Diet on Pharmacokinetics of Norfloxacin in Beagle Dogs

目的:研究脂质饮食对诺氟沙星在Beagle犬体内药动学的影响。方法:取6只Beagle犬均分为两组,分别在空腹或进食脂质状态下灌服诺氟沙星胶囊40 mg/kg,2周后两组犬交叉实验;采用高效液相色谱法测定给药前与给药后0.5、1、2、3、4、6、8、10、12、24 h的血药浓度,用3p97软件计算诺氟沙星的药动学参数。结果:诺氟沙星在Beagle犬空腹和进食脂质状态下的药-时曲线均符合一室模型;空腹和进食脂质状态下诺氟沙星的主要药动学参数分别为t1/2(3.82±1.10)、(4.30±1.78)h,tmax(0.72±0.37)、(2.94±1.12)h,cmax(0.93±0.18)、(0.92±0.43)μg/ml,AUC0-24 h(6.26±0.98)、(8.45±1.78)μg·h/ml;两种状态间比较,除tmax差异有统计学意义(P<0.01)外,其余参数差异无统计学意义(P>0.05)。结论:脂质饮食可明显延迟诺氟沙星的达峰时间。

OBJECTIVE： To study the effects of lipid diet on pharmacokinetics of norfloxacin in Beagle dogs. METHODS： 6 Beagle dogs were divided into 2 groups, and then given norfloxacin 40 mg/kg under the condition of empty stomach or with lipid diet for 2 weeks. The crossover experiment of 2 groups was carried out after 2 weeks. The blood concentration of norfloxacin was determined by HPLC before and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 h after medication, and pharmacokinetic parameters ofnorfloxacin under the condition of empty stomach or with lipid diet were calculated by using 3p97 software. RESULTS ： The blood concentration-time curves of norfloxacin were up to one-compartment model under the condition of empty stomach or with lipid diet. Main pharmacokinetic parameters of norfloxacin under the condition of empty stomach vs. with lipid diet were as follows： t1/2： （3.82 ± 1.10） h vs. （4.30±1.78）h; tmax（0.72± 0.37）h vs. （2.94± 1.12）h; cmax （0.93±0.18） μg/ml vs. （0.92 ±0.43） μg/ml;AUC0-24h： （6.26 ±0.98） μg. h/ml vs. （8.45 ± 1.78） μg. h/ml, respectively. There was statistical significance in pharmacokinetic parameters of tmax （P〈0.01）, while there was no statistical significance in other parameters （P〉0.05）. CONCLUSIONS： Lipid diet can delay tmax of norfloxacin significantly.