Gastric penetration of amoxicillin in a human Helicobacter pylori-infectedxenograft model

The delivery of antibiotics into Helicobacter pylori-infected human stomach s is still poorly understood. Human embryonic gastric xenografts in nude mi ce have recently been proposed as a new model for the study of H. pylori in fection. Using this model, we compared the penetration of amoxicillin, afte r intraperitoneal administration of a dose of 20 mg/kg of body weight, into the gastric mucosae of infected and uninfected xenografts. The concentrati ons of this drug in serum and superficial gastric mucosae were determined a t 20 min and 1 and 3 h after injection. Ten mice with H. pylori-infected gr afts (n = 5) or uninfected grafts (n = 5) were studied. Mucosal samples wer e obtained by cryomicrotomy. The concentrations in serum were similar to th ose obtained in the serum of humans after oral administration of 1 g of amo xicillin. The mean area under the tissue concentration-versus-time curve fr om 0 to 3 h obtained for mice with infected grafts was significantly higher than that obtained for the animals with uninfected grafts (P = 0.01). Thes e results suggest that the penetration of amoxicillin into the superficial gastric mucosa may be substantially increased in the case of H. pylori infe ction. Thus, human xenografts in nude mice represent a new, well-standardiz ed model for investigation of systemic delivery of drugs into H. pylori-inf ected gastric mucosa.