The stability of amoxycillin, clarithromycin and metronidazole in gastric juice: Relevance to the treatment of Helicobacter pylori infection
The stability of amoxycillin, clarithromycin and metronidazole in gastric juice: Relevance to the treatment of Helicobacter pylori infection
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DOI：
10.1093/jac/39.1.5
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发表时间：
1997-01-01
影响因子：
5.2
通讯作者：
Spiller, RC
中科院分区：
文献类型：
--
作者：
Erah, PO;Goddard, AF;Spiller, RC
虽然奥美拉唑是使用克拉霉素、阿莫西林和甲硝唑的抗幽门螺杆菌治疗方案中的重要组分，但其增强抗菌作用的机制尚不清楚。该效应的一个潜在解释是联合给予奥美拉唑诱导胃pH值变化导致抗生素化学稳定性增加。研究了克拉霉素、阿莫西林和甲硝唑在奥美拉唑7天疗程前后采集的水溶液和人胃液中的化学稳定性。阿莫西林，克拉霉素和甲硝唑在pH 1.0至8.0的缓冲水溶液和pH 2.0和7.0的胃液中制备。胃液样品取自禁食的H.幽门螺杆菌阴性志愿者在接受奥美拉唑7天疗程之前和之后。将所有样品在37 ° C下孵育，并通过HPLC间隔分析。阿莫西林、克拉霉素和甲硝唑分别在pH4.0 -7.0、pH5.0 -8.0和pH2.0 -7.0的水溶液中稳定。在pH 2.0时，降解半衰期分别为19.0 +/- 0.2 h、1.3 +/- 0.05 h和2200 +/- 1100 h。在pH 2.0的胃液样品中，降解半衰期分别为15.2 +/- 0.3 h、1.0 +/- 0.04 h和大于或等于800 h。在pH 7.0的胃液样品中药物的半衰期均>68 h。奥美拉唑与阿莫西林或克拉霉素联合给药可能会增加阿莫西林和克拉霉素在胃液中的化学稳定性。克拉霉素在正常胃pH值（1.0-2.0）下迅速降解，但阿莫西林和甲硝唑在此pH值下足够稳定，可在胃中保持抗菌浓度。
Although omeprazole is an important component in anti-Helicobacter pylori therapeutic regimes using clarithromycin, amoxycillin and metronidazole, the mechanism by which it enhances antimicrobial action is unknown. One potential explanation for this effect is increased antibiotic chemical stability resulting from gastric pH changes induced by coadministration of omeprazole. The chemical stability of clarithromycin, amoxycillin and metronidazole was investigated in aqueous solutions and in human gastric juice collected before and after a 7-day course of omeprazole. Amoxycillin, clarithromycin and metronidazole were prepared in buffered aqueous solutions of pH 1.0 to 8.0 and in gastric juice of pH 2.0 and 7.0. The gastric juice samples were obtained from fasted H. pylori-negative volunteers before and after they had received a 7-day course of omeprazole. All the samples were incubated at 37 degrees C and analysed at intervals by HPLC. Amoxycillin, clarithromycin and metronidazole were stable in aqueous solutions of pH 4.0-7.0, pH 5.0-8.0 and pH 2.0-7.0, respectively. At pH 2.0, the degradation half-lives were 19.0 +/- 0.2 h, 1.3 +/- 0.05 h and 2200 +/- 1100 h, respectively. In gastric juice samples of pH 2.0, the degradation half-lives were 15.2 +/- 0.3 h, 1.0 +/- 0.04 h and greater than or equal to 800 h, respectively. The half-lives of the drugs in the gastric juice samples of pH 7.0 were all >68 h. The co-administration of omeprazole with amoxycillin or clarithromycin is likely to increase the chemical stability of amoxycillin and clarithromycin in gastric juice. Clarithromycin degrades rapidly at normal gastric pH (1.0-2.0) but amoxycillin and metronidazole are sufficiently stable at this pH to maintain an antibacterial concentration in the stomach.