PK/PD Evaluation for two Heliobacter pylori therapies

• Grant number: 01/10065-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: October 01, 2003
• End date: January 31, 2008
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: José Pedrazzoli Júnior
• Grantee: José Pedrazzoli Júnior
• Host Institution: Centro de Ciências Biológicas e da Saúde. Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Background aims: Helicobacter pylori colonization of the gastric mucosa has been considered the most common chronic bacterial infection in humans. It produces progressive gastric damage and it has been associated with gastro duodenal ulcers, adenocarcinoma and lymphoma of the stomach, being considered a type I carcinogen. Most importantly, Helicobacter pylori eradication modifies the natural history of peptic ulcer disease, and is strongly recommended for the treatment of peptic ulcer disease, bleeding peptic ulcer, low-grade gastric Iymphoma, severe gastritis and following resection of early gastric cancer. Our present knowledge of the treatments for eradicating H. pylori is based on the results of clinical trials involving a combination of two or more drugs, with the efficacy of the drug combinations being determined by trial and error. The development of a simple, safe and effective therapeutic regimen requires knowledge of the pharmacology of the agents to be used and should consider simplicity, adverse effects, antimicrobial sensitivity, antimicrobial levels at infection site drug synergism, as well as host and pathogen characteristics. Several factors related to the success or failure of a given antibiotic therapy have been already described and validated but have not been carefully explored for Helicobacter pylori eradication therapy. Among these are AUC/MIC, time above MIC, Cmax/MIC ratio, an evaluation of antibiotic interaction during treatment (synergy, antagonism or additivity) and impact of innoculum size. Aims to examine, during a real treatment situation, factors potentially associated with treatment success or failure. The following criteria will be evaluated: AUC/MIC, time above MIC, Cmax/MIC ratio, resistance to administered drugs and impact of innoculum size for the two most recommended treatment schedules. Methods: eighty individuals with Helicobacter pylori infection will be included. They will be randomly assigned to two treatment groups: (A) PPI, plus amoxicillin and clarithromycin and (8) bismuth subcitrate plus tetracycline and the treatment period will consist of 10 days for both groups. The antimicrobial contend in gastric juice and blood will be measured at treatment begin, middle and end of treatment. The following parameters will be evaluated for both treatments: AUC/MIC, time above MIC, Cmax/MIC ratio, resistance and innoculum size... (AU)