抗幽门螺杆菌药物在大鼠胃内的分布和雷贝拉唑的影响

The transport of antibiotics used against Helicobacter pylori in rat stomach and the effects of rabeprazole

目的研究以雷贝拉唑、阿莫西林、左氧氟沙星组成的抗幽门螺杆菌(H.pylori)感染三联疗法中抗生素在大鼠胃内转运、分布特点及雷贝拉唑对其药动学和胃内转运的影响。方法建立大鼠胃内抗生素转运模型,给予相应药物后按时间点分别收集血浆、胃液、胃黏膜组织样本,采用高效液相色谱法检测各样本中抗生素的浓度,计算药物分布转运的药代动力学参数。结果大鼠血浆中阿莫西林半衰期(T1/2)约为1 h,雷贝拉唑对阿莫西林的药代动力学参数没有显著影响,但延长了左氧氟沙星的T1/2。阿莫西林在胃中的浓度显著低于血浆中的浓度,而左氧氟沙星在胃液中浓度比血浆中高。前胃黏膜中两种抗生素浓度低于腺胃黏膜中浓度,而抗生素在腺胃黏膜中不同区域浓度差异无统计学意义。结论抗H.pylori抗生素阿莫西林和左氧氟沙星能够从血中跨胃黏膜转运到胃中,但胃内不同区域胃黏膜中的浓度存在差异;胃内可能具有左氧氟沙星主动转运机制。左氧氟沙星药动力学参数受到了雷贝拉唑的影响。

Objective To explore the characteristic of amoxicillin and levofloxacin in the transport and distribution in rat stomach in the triple therapy including rabeprazole used against Helicobacter pylori （ H. pylori） and the effect of rabeprazole on their pharmacokinetics. Methods The model for exploring the antibiotics transport and distribution in rat stomach was prepared. The different sample in rat including blood, the different region gastric mucosa, and the total gastric juice were obtained in the different time point after administration. The antibiotic concentrations in the different sample were surveyed by high performance liquid chromatography （ H. PYLORILC） . The statistical analysis of the pharmacokinetics parameters of the drugs transport and distribution were carried out. Results The amoxicillin T1/2 in rat blood was 1 h or so. Rabeprazole did not significantly change the pharmacokinetic parameters of amoxicillin in the plasma, and lengthened the levofloxacin T1/2 in the plasma. Amoxicillin concentration in rat stomach was lower significantly than that in the plasma. Levofloxacin concentration in rat gastric juice was higher than that in the plasma. The two antibiotics concentration in the forestomach mucosa was lower than that in the glandular stomach mucosa. The deviation of two antibiotics concentration in the different region of the glandular stomach mucosa was not statistical significance. Conclusion The antibiotic amoxicillin and levofloxacin used against H. pylori could penetrate the gastric mucosa into the stomach. The antibiotic concentration in gastric mucosa in the different regions is different. The active transport mechanism of the transporting levofloxacin could exist in the stomach. Rabeprazole could affect levofloxacin kinetic parameter in blood or gastric mucosa.