title: Local gastric and serum amoxicillin concentrations after different oral application forms.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: M P
authors.initials: MP
authors.lastname: Cooreman
authors.forename: P
authors.initials: P
authors.lastname: Krausgrill
authors.forename: K J
authors.initials: KJ
authors.lastname: Hengels
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000658:Amoxicillin / Q000097:blood* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D008297:Male
chemical_list: D000658:Amoxicillin