Cooreman M P, Krausgrill P, Hengels K J
Department of Gastroenterology, Heinrich-Heine-Universität, Düsseldorf, Germany.
Antimicrob Agents Chemother. 1993 Jul;37(7):1506-9. doi: 10.1128/AAC.37.7.1506.
The high recolonization rate after monotherapy of Helicobacter pylori-positive gastritis may be due to insufficient local drug concentrations. To investigate the role of local diffusion, we measured levels of amoxicillin, a drug with good in vitro activity against H. pylori, in the mucosa and serum. One gram of amoxicillin was given to healthy volunteers as a tablet (n = 6) or as water-dissolved, fizzing "Tab" (n = 6). Gastroscopy with biopsies from the antrum, corpus, and fundus was performed at 30, 60, and 90 min. Concentrations in the mucosa were measured after homogenization with the agar diffusion method using Bacillus subtilis as the biological indicator. Serum samples, taken basally and every 15 min, were analyzed by high-pressure liquid chromatography. Drug levels in the fundus and corpus remained far below those in the antrum for both application forms. The highest concentrations were reached after 30 min, with bactericidal levels in the antrum in two of six subjects who took the tablet form and five of six subjects who used Tabs. At 60 and 90 min, almost all values were below the MBC for 90% of the strains tested. The concentrations in serum, however, rose continuously, to reach a maximum after 75 or 90 min. These results show that incomplete elimination may be due to subbactericidal concentrations of antibiotics with high in vitro efficiency at the desired site of action in vivo and that local diffusion in the mucosa is essential for therapeutic effectiveness against H. pylori.
幽门螺杆菌阳性胃炎单药治疗后再感染率高可能是由于局部药物浓度不足。为了研究局部扩散的作用，我们测量了阿莫西林（一种对幽门螺杆菌具有良好体外活性的药物）在黏膜和血清中的水平。给健康志愿者口服1克阿莫西林片剂（n = 6）或水溶泡腾片“Tab”（n = 6）。在30、60和90分钟时进行胃镜检查，并从胃窦、胃体和胃底取活检组织。用枯草芽孢杆菌作为生物指示剂，采用琼脂扩散法将黏膜样本匀浆后测量其中的浓度。基础样本以及每隔15分钟采集的血清样本通过高压液相色谱法进行分析。两种剂型的胃底和胃体中的药物水平均远低于胃窦中的水平。两种剂型在30分钟后均达到最高浓度，服用片剂的6名受试者中有2名、使用泡腾片的6名受试者中有5名胃窦中的药物浓度达到杀菌水平。在60和90分钟时，几乎所有数值均低于所测试90%菌株的最低杀菌浓度。然而，血清中的浓度持续上升，在75或90分钟后达到最高值。这些结果表明，不完全清除可能是由于在体内所需作用部位抗生素浓度低于杀菌水平，尽管其在体外效率较高，并且黏膜中的局部扩散对于抗幽门螺杆菌的治疗效果至关重要。
