Impact of acid secretion, gastritis, and mucus thickness on gastric transfer of antibiotics in rats

Abstract

Background and aims: The success of Helicobacter pylori eradication regimens depends on gastric pH, inflammation, and mucus thickness. Our aim was to investigate the effects of acid secretion, inflammation, and mucolysis on gastric antibiotic transfer. Subjects and methods: A total of 134 anaesthetised rats were given metronidazole, amoxicillin, or clarithromycin intravenously and gastric contents were aspirated via an indwelling cannula. Acid secretion was controlled by either omeprazole or pentagastrin while gastritis was induced by infection with H pylori or dosing with iodoacetamide. Mucolysis was achieved by instilling pronase into the gastric lumen. Results: Metronidazole transfer increased with acid secretion and fell with omeprazole, independently of gastric pH. Clarithromycin was also transferred with acid but was then rapidly degraded. Omeprazole prevented this degradation, raising gastric luminal concentrations. Omeprazole did not alter amoxicillin transfer. Gastritis induced by H pylori did not alter gastric transfer of metronidazole and amoxicillin but that of clarithromycin was increased by 23%. However, gastritis induced by iodoacetamide reduced clarithromycin transfer without any effect on metronidazole or amoxicillin transfer. Pronase treatment increased amoxicillin transfer fourfold and metronidazole by 66% but reduced clarithromycin transfer by 35%. Conclusions: Metronidazole and clarithromycin are predominantly transferred with gastric acid rather than by an acid trapping mechanism. Pronase increases the appearance of amoxicillin and metronidazole in gastric secretions.

Transfer and distribution of amoxicillin in the rat gastric mucosa and gastric juice and the effects of rabeprazole

“…The anaesthetized rat model provides an opportunity to investigate the mechanisms of gastric antibiotic transfer. In contrast to human studies, no pyloric loss or bile contamination of gastric juice and mucosa occurs, and the gastric transport of novel compounds can be readily evaluated [18] . The blistering method of dissecting the gastric mucosa ensures that the mucosa sample is not contaminated by blood in the micrangium below the gastric mucosa.…”

“…In the present experiments, three different doses, high (200 mg/kg), middle (100 mg/kg) and low (50 mg/kg), were adopted to avoid the possibility of insufficient dosage, and an animal model was modified according to reported methods [11,18,30] . The anaesthetized rat model provides an opportunity to investigate the mechanisms of gastric antibiotic transfer.…”

“…Gastric clearance=∑(Gastric juice volume per min × antibiotic concentration) 0-2 h /Plasma AUC 0-2 h [18] .…”

Efficacy and Pharmacological Mechanism of Pronase-Enhanced Low-Dose Antibiotics for Helicobacter pylori Eradication

“…In our study, we also detected the concentrations of clarithromycin in gastric tissue and serum according to previous studies (10,22). However, the peak area is very small, and detection is not sufficiently sensitive.…”

“…It also increased the amoxicillin transfer rate from plasma to gastric aspirate by traversing the gastric mucosa (10). Here, pronase alone exhibited no inhibitory effect on H. pylori, although it has been reported that pronase has an effect on promoting the eradication of H. pylori.…”