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 BaciUlus 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. pylor.Worldwide and in all age groups, Helicobacterpylori is the major etiologic factor in chronic active antral gastritis (8,9,20,28). There is also convincing evidence that H. pylon plays an important role in duodenal ulcer disease (2, 5, 12), especially since eradication of the bacterium is associated with a significantly lower recurrence rate compared with H2 receptor blocker therapy (6,13,19). Moreover, in up to 70% of patients with nonulcer dyspepsia, H. pylon-positive active antral gastritis can be diagnosed (18,25), and although controversy about the clinical relevance of chronic gastritis remains, several investigators have found that these patients profit from elimination of H. pylon in terms of symptomatic improvement (14,26). Bismuth salts, like colloidal bismuth subcitrate, and a variety of antibiotic drugs are able to eliminate the bacterium from the antral mucosa (15, 23), but recolonization within 1 month after therapy is the rule (24, 25). The reason for this incomplete elimination has not been sufficiently elucidated; it may be due either to reinfection from a bacterial reservoir in the upper gastrointestinal tract or to subbactericidal drug concentrations at the desired site of action during therapy. To investigate the latter possibility, we measured gastric mucosal concentrations of amoxicillin, a drug with excellent in vitro activity against H. pylori, given in the usual therapeutic dosage of 1 g in tablet form or in water-dissolved form. To compare the role of local diffusion of the drug with its systemic availabi...

Formulation and evaluation of oil entrapped gastroretentive floating gel beads of loratadine

“…Seventy mL of each test medium (water, 0.1 mol L -1 HCl, acid phthalate buffer, pH 3.12 and normal saline) was separately agitated on a magnetic stirrer at 75 rpm and 37°C and 1 g of the floating beads were incorporated into the test medium (6). The lag time to float and the floating behavior of the beads in each test medium were observed for a period of 12 h.…”

Formulation and In Vitro evaluation of pH sensitive oil entrapped buoyant beads of amoxicillin.

“…filled in a capsule (# 2) was used as a reference formulation. Drug release data were corrected for the values of the drug loss during sampling [17].…”

“…Floating drug delivery systems have a bulk density lower than gastric fluids and thus remain buoyant in the stomach for a prolonged period of time, without affecting the gastric emptying rate. While the system is floating on the gastric contents, the drug is released slowly at a desired rate from the system and remaining part of the residual system is slowly emptied from the stomach and enhanced GRT of the drug [5][6][7]. This study was envisaged to develop mucoadhesive gastric retentive formulation of amoxicillin in order to achieve targeted release of doi:10.5138/ ijdd.2010.0975.0215.03062 ©arjournals.org, All rights reserved.…”

In vivo Evaluation of Amoxicillin Trihydrate and Clarithromycin-Loaded Mucoadhesive Microspheres for H. pylori Eradication

“…Incomplete eradication of H. pylori is mainly due to the short residence time of antimicrobial agents in the stomach so that effective antimicrobial concentration cannot be achieved in the gastric mucous layer or epithelial cell surfaces where H. pylori exists [8,9].…”