Objective: To evaluate the effect of pronase on amoxicillin and metronidazole concentrations in gastric tissue.
Methods: C57BL/6 mice were randomly divided into experimental group (n = 70) and control group (n = 70). Amoxicillin (28.6 mg/kg), metronidazole (22.5 mg/kg) and omeprazole (138.2 mg/kg) were administered orally to C57BL/6 mice, combined with pronase (110 mg/kg) or same amount of sterile PBS. Gastric tissue and blood plasma samples were taken at 10 point-in-time (7 mice/time) from 15 min up to 360 min after administration. Concentrations of amoxicillin and metronidazole were detected by high performance liquid chromatography. Gastritis index of gastric mucosa (hematoxylin-eosin staining) and the gastric tissue expressions of mucin 5AC (Western blot) were detected at 120 min and 360 min after administration.
Results: The time to peak concentration of amoxicillin and metronidazole in gastric tissue appeared earlier than that in blood plasma (15 min vs 60 min). Tissue concentrations of amoxicillin and metronidazole of experimental group were significantly higher than those of control, and they were mainly at 15 min to 90 min (P < 0.05). Plasma concentrations of amoxicillin and metronidazole of experimental group at 15 min and 30 min were higher than those of control (P < 0.05). There was no difference in gastritis index between experimental group and control at 120 min and 360 min after administration (0.28 ± 0.18 vs 0.14 ± 0.14, P > 0.05; 0.43 ± 0.20 vs 0.28 ± 0.18, P > 0.05). The expressions of mucin 5AC in experimental group were lower than those of control (0.036 ± 0.006 vs 0.197 ± 0.058; P < 0.05; 0.039 ± 0.008 vs 0.208 ± 0.072, P < 0.05).
Conclusions: Pronase can significantly enhance the drugs penetration from mucus into gastric tissue. Concentrations of amoxicillin and metronidazole of experimental group in local gastric tissue and plasma are higher than those of control, especially in improving concentrations of gastric tissue and prolongation of exposed time.